|
Mark
A. JOBLING (UK)
Molecular
Anthropology in the Genomic Era
University of Leicester, UK
The
first attempts to understand the history of human population movement,
demographic change and admixture through genetics used protein markers,
such as blood groups and HLA. We now suspect that the diversity of
these markers is strongly influenced by natural selection, and
researchers interested in investigating the human past have since then
sought neutral markers, regarding phenotypes and adaptive influences as
a nuisance.
Prominent amongst these
markers have been the non-recombining region of the Y
chromosome and mitochondrial (mt) DNA, despite ongoing concerns about
regional selection on the latter, and most major questions and many
populations have now been addressed to some degree using small numbers
of informative sites on these loci. Their uniparental modes of
inheritance continue to illuminate sex-biased processes, and the
coinheritance of Y haplotypes with patrilineal surnames allows the
exploitation of these cultural labels in the investigation of past
population structures.
Issues of ascertainment
bias of markers here are fading with the use of multiple
Y-STRs and increasing numbers of Y-SNPs, and with increased resolution
of mtDNA analysis. While the mtDNA resolution limit has been reached
now that its 16.5kb can be sequenced readily in many individuals, this
is not so with the Y - only a small number of the available STRs is
normally analysed, and resequencing of megabases of this chromosome is
now possible with careful application of new technologies. This reveals
100s of new SNPs per chromosome analysed, posing challenges for
unifying datasets and standardising methodology and nomenclature.
Recent sequence analyses of Y chromosomes separated by only a few
generations identifies lineage-specific markers (Xue et al., 2009),
perhaps promising the phylogenetic resolution needed to distinguish
between different migration events very close in time. Members of the
general public, through their obsessions with genetic genealogy, are
contributing useful scientific insights.
Genome-wide SNP typing is now
affordable and offers interesting insights into the geographical
patterning of common autosomal variation (Novembre et al., 2008). It
suffers from the Eurocentric ascertainment bias of common SNPs, and a
similar bias in the population distribution of available genome-wide
association study data (Need & Goldstein, 2009). Because of the
tag-SNP-based designs of marker sets, it also lacks much of the
potential temporal resolution provided by the evolutionary
relationships among haplotypes. Conventional resequencing of multiple
specific X-chromosomal and autosomal segments, and the typing of
markers in low-recombination regions, can provide some of this
resolution, and has thrown light on the history of sex-specific
behaviours (Hammer et al., 2008).
Using genetics to test hypotheses
based on historical, archaeological or linguistic evidence often uses a
cherry-picking approach to the other disciplines that lacks
objectivity. Although most of the tractable questions seem likely to be
those linked to relatively recent events, one of the most impressive
findings of recent years has been the remarkable explanatory power of
simple distance from East Africa for patterns of modern genetic
diversity (Handley et al., 2007), underscoring the importance of early
events when populations were small.
By contrast, there are researchers
who regard phenotypes and selection as the important stuff, and
population structure and history as the distracting nuisance.
Unfortunately, although the phenotypes of humans are of particularly
acute interest, our species is not a model organism. The kinds of
controlled experiments we might carry out on mice are impossible, so we
must make do with the 'experiments of nature' represented by
anthropologically interesting populations, while at the same time
trying to account for the complex influence of a complex environment
that includes the epitome of defining human complex phenotypes,
culture.
Some anthropologically interesting
phenotypes are yielding to the power of genetic and genomic analysis,
including resistance or susceptibility to some pathogens, dietary
adaptation, pigmentation, hair thickness and tooth morphology (Kimura
et al., 2009), and the fascinating (no, seriously) trait of earwax type
(Yoshiura et al., 2006). Other traits promise to be less tractable,
with the tractability depending on the often unknown underlying genetic
architecture. Stature is a good example - in outbred populations in the
developed world, dozens of loci have been identified in huge samples,
but each contributes only a tiny amount (a few millimetres) of the
variance of the trait. Tellingly, Francis Galton's Victorian
back-of-an-envelope approach to height prediction greatly outperforms
the technological might of twenty-first century genomics (Aulchenko et
al., 2009). Here, the common-disease-common-variant hypothesis seems to
be losing the battle to hypothetical copy-number variants, rare
mutations, gene-gene interactions and epigenetics (Manolio et al.,
2009).
Short stature among pygmy populations
is a well-known example of an anthropologically interesting phenotype,
but its elucidation falls foul of the problem of unknown genetic
architecture, both within and between populations. If one or a few loci
explain it, and if candidate loci translate from Europe to the rest of
the world, then simple approaches may bear fruit. But if, as seems
likely, the trait is complex and multigenic, then it will more
difficult to understand. We may hypothesise a common origin of pygmy
groups to explain the common phenotype, but this would make it
difficult to pinpoint the specific locus or loci responsible for the
phenotype amongst the loci shared simply through recent common origin.
Then again, the detection of phenotypically important loci within
populations will be difficult because of small sample sizes, and grant
applications (often damned by reviewers as 'fishing expeditions') will
tend to founder upon the unforgiving reefs of power calculations.
The role of natural selection in the
development of short stature is mysterious, and it is difficult to
regard selective explanations based on the ease of moving about in
forests as anything but ludicrous 'Just So' stories. Darwin would
probably advocate sexual selection here, but proving him right is not
going to be easy. Even when we can see clear selective advantages to
particular adaptation, the problem of drift is a bugbear of studies of
poorly understood phenotypes. We can use genome-wide approaches to seek
segments of DNA showing frequency elevations in populations living, for
example, at high altitude, but how do we distinguish between adaptation
and drift as explanations for frequency differences? And can we
identify suitable control populations, in which drift has not also been
a problem? If we want to support findings by 'replication' in other
high-altitude populations, we face the problem that the adaptation may
have arisen independently, and may even have a different physiological
and genetic basis. It seems likely that admixture-based approaches will
be useful here.
In the sunlit distance, glimpsed
through a glass darkly, lies the brave and bright new world of whole
genome sequences (www.1000genomes.org), unsullied by ascertainment bias
and rich with rare variants. Although the new methods are still too
expensive to be applied to most anthropologically interesting samples,
this is likely to change soon, and molecular anthropologists should
learn how to mine and use such sequences, and think what questions they
would like to address with them. Surely, the more sequence, the better?
If we knew the sequences of all the genomes of everyone, we'd be able
to learn everything that could be learned about the relationships among
individuals and populations, the processes of mutation, and the
influence of selection. It seems likely that the recording and
classifying of the environments and the phenotypes (Samuels et al.,
2009), rather than the genotypes, will then become crucial, and the
anthropologists (and the ethicists) will inherit the world.
References:
Aulchenko Y.S., Struchalin M.V., Belonogova N.M., Axenovich T.I.,
Weedon M.N., Hofman A., Uitterlinden A.G., Kayser M., Oostra B.A., van
Duijn C.M. et al. (2009) Predicting human height by Victorian and
genomic methods. Eur. J. Hum. Genet., 17: 1070-1075.
Hammer M.F., Mendez F.L., Cox M.P., Woerner A.E. & Wall J.D. (2008)
Sex-biased evolutionary forces shape genomic patterns of human
diversity. PLoS Genet., 4: e1000202.
Handley L.J., Manica A., Goudet J. & Balloux F. (2007) Going the
distance: human population genetics in a clinal world. Trends Genet.,
23: 432-439.
Kimura R., Yamaguchi T., Takeda M., Kondo O., Toma T., Haneji K.,
Hanihara T., Matsukusa H., Kawamura S., Maki K. et al. (2009) A common
variation in EDAR is a genetic determinant of shovel-shaped incisors.
Am. J. Hum. Genet., 85: 528-535.
Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A.,
Hunter D.J., McCarthy M.I., Ramos E.M., Cardon L.R., Chakravarti A. et
al. (2009) Finding the missing heritability of complex diseases.
Nature, 461: 747-753.
Need A.C. & Goldstein D.B. (2009) Next generation disparities in
human genomics: concerns and remedies. Trends Genet., 25: 489-494.
Novembre J., Johnson T., Bryc K., Kutalik Z., Boyko A.R., Auton A.,
Indap A., King K.S., Bergmann S., Nelson M.R. et al. (2008) Genes
mirror geography within Europe. Nature, 456: 98-101.
Samuels D.C., Burn D.J. & Chinnery P.F. (2009) Detecting new
neurodegenerative disease genes: does phenotype accuracy limit the
horizon? Trends Genet., 25: 486-488.
Xue Y., Wang Q., Long Q., Ng B.L., Swerdlow H., Burton J., Skuce C.,
Taylor R., Abdellah Z., Zhao Y. et al. (2009) Human Y chromosome
base-substitution mutation rate measured by direct sequencing in a
deep-rooting pedigree. Curr. Biol., 19: 1453-1457.
Yoshiura K., Kinoshita A., Ishida T., Ninokata A., Ishikawa T., Kaname
T., Bannai M., Tokunaga K., Sonoda S., Komaki R. et al. (2006) A SNP in
the ABCC11 gene is the determinant of human earwax type. Nat. Genet.,
38: 324-330.
|
Jorge
ROCHA (Portugal) (1) (2)
The
peopling of Africa
(1) IPATIMUP-Institute of Pathology and
Molecular Imunology of the University of Porto.
(2) Department of
Zoology and Anthropology, Faculty of Sciences, University of Porto.
[Figure not reported
here]
Despite Africa's central role in human evolution, African populations
have been less well characterized than other groups in most studies
addressing human genetic variation. Until recently, inferences about
human population history typically relied on few African populations
that were assumed to be representative of the whole continental
diversity. While this limitation did not challenge the validity of
general conclusions about the origins and global distribution of human
genetic variability, insufficient sampling has certainly hampered our
perception of how human diversity was shaped within Africa. With the
highest time depth of human history and over 2000 ethnolinguistic
groups dwelling in landscapes that range from the driest deserts to the
most humid forests, Africa could hardly be understood without a more
comprehensive population sampling.
In the last decade, improvements in sampling coverage, together with
the increasing availability of highly informative genetic markers and
the use of new approaches to data analysis, had a tremendous impact in
the assessment of Africa's genetic variation. Although the amount and
quality of genetic data is still far from being fully satisfactory, the
current genetic portrait of Africa has reached an unprecedented level
of precision. The aim of this lecture is to provide an overview of the
genetic evidence on African population history that became available
with these recent advances.
A significant part of our present understanding of African genetic
variation is based on the study of mitochondrial DNA (mtDNA) and the
non-recombining portion of the Y chromosome (NRY) (Cruciani et al.,
2002; Salas et al., 2002). Because of their uniparental patterns of
inheritance and lower effective population size, mtDNA and NRY
haplotypes provide complementary information about female- and
male-specific aspects of genetic variation and are especially sensitive
to the effects of drift. MtDNA and NRY markers tend to be highly
geographically structured and, due to lack of recombination, haplotype
phylogenies can be easily reconstructed, providing a temporal framework
for mutation accumulation, which can be related to the geographic
distribution of different lineages. Several NRY and mtDNA haplogroups
are particularly informative because their origins appear to be
geographically and temporally distinct from each other. For example,
the distribution of the oldest basal NRY-haplogroup A-M91 suggests an
ancestral link of the southern African Khoe-San click-speaking groups
to East Africa. The relatively old NRY B2b-M112 haplogroup points to
the common ancestry of Khoe-San and Pygmy hunter-gatherer groups. A
lineage within the younger E3b-M35* paragroup suggests that pastoralism
might have been introduced to southern African from East Africa prior
to Bantu migrations. The relatively young E3a-M2 haplogroup is
widespread in Niger-Kordofonian-speaking populations and provides a
marker for the expansion of Bantu-speaking agriculturists. Among the
mtDNA haplotypes, the basal L0d clade is almost exclusive to the
southern African Khoe-San but is also found in the click-speaking
Sandwe from Tanzania confirming the ancient link of the Khoe-San to
Eastern Africa. The younger haplogroup L1c, which probably originated
in central Africa, is crucial to assess the ancestral relationship
between western Pygmy hunter-gatherers and their neighboring
Bantu-speaking farmers. However, an important limitation of studies
based on the NRY an mtDNA markers is that they amount to the
characterization of only two genetic systems, which, due to the
stochasticity of evolutionary processes, are insufficiently robust to
generate meaningful estimates of relevant population history
parameters. Multilocus approaches designed to overcome this difficulty
have received a remarkable boost with the recent publication of Sarah
Tishkoff's landmark study on 2432 individuals from 113 populations
using a panel of 1327 polymorphic markers (Tishkoff et al., 2009).
In brief, the study as shown that most African genetic variation can be
sorted into 14 ancestral population clusters and that most populations
exhibited high levels of mixed ancestry, consistent with historical
migrations across the continent. Consideration of geographic data along
with clustering analysis distinguished five major groups of clusters,
including (Fig. 1): i) a contiguous northern fringe encompassing
Berber, Cushitic and Semitic Afroasiatic speakers from Saharan and East
Africa; ii) a widespread group corresponding to the distribution of the
Niger-Kordofonian language family (paralleled by the distribution of
NRY haplogroup E3a-M2); iii) another group comprising Chadic and
Nilo-Saharan-speaking populations from Nigeria, Cameroon, Chad and
southern Sudan (some of which share a lineage within NRY haplogroup R
that may have been introduced into Africa by a back migration
originating in Asia; Cruciani et al., 2002); iv) a group with
Nilo-Saharan and Cushitic-speaking populations from Sudan, Kenya and
Tanzania; and v) a group with noncontiguous geographic distribution
consisting of Pygmy and southern Africa Khoe-San populations, providing
evidence for shared ancestry among hunter-gatherers (consistent with
the distribution of NRY haplogroup B2b, but not with mtDNA, since
haplogroup L1c seems to preferentially link Western Pygmies to
neighboring Bantu agriculturists). In spite of the major advance
provided by this study, it is important to note that regions like the
Sahel, the Atlantic West Africa, Namibia, Angola and the central corridor
comprising the DR of Congo, Central Zimbabwe and the Zambia, remain
sparsely sampled. On the other hand, to make full use of the framework
provided by Tishkoff's investigation, it is crucial to generate
increasingly comparable datasets. This could be achieved by defining a
minimum subset of highly informative markers to be used in future works
about other African populations.
To disentangle the spatial-temporal processes that gave rise to the
emergent portrait of African genetic diversity, it will be important to
address both deep-time and more fine-scale questions, combining
continent-wide studies with more detailed pictures provided by regional
or local case studies. Moreover, an interesting approach to interpret
the basic properties of the observed genetic variation is to focus on
discordance among different sets of genetic data, or between genetic
data and non-genetic aspects of human variation. For example, the
discrepancy between the patterns of genetic variation in NRY and mtDNA
has provided important insights about the influence of sociocultural
factors in shaping differences in male and female migration rates and
effective sizes (Destro-Bisol et al., 2004). Discordance between levels
and patterns of genetic variation in nuclear and uniparental markers
may be useful to reduce the number of population history models that
are compatible with the data. On the other hand, differences between
geographic patterns at putatively selected loci and neutral loci may be
used to evaluate the strength of selection and to analyze the influence
of demographic processes in spreading selected variants (Coop et al.,
2009). Finally, dissociation of common trends in the relationships
between genetics, linguistics and lifestyles provide unique
opportunities to analyze the impact of admixture between different
populations and to analyze how major shifts in genetic and cultural
patterns occur. For example, interactions among the peoples of southern
Angola, which has become one my own research interests, has generated
intriguingly discordant combinations of ethnicity, language and
lifestyle that will be discussed in the lecture to illustrate the
usefulness of local patterns in understanding major tendencies (Coelho
et al., 2009).
A final aspect of the recent advances in understanding genetic
diversity within Africa is related with data analysis. Datasets based
on multiple, independently evolving genetic systems are particularly
well suited to simulation-based inferential frameworks that are aimed
to distinguish between alternative models of population history and to
estimate key microevolutionary parameters under a given model. Recent
applications of rejection algorithms and Approximate Bayesian
Computation to infer the branching history of Pygmy and agricultural
populations provide excellent examples of the usefulness of new
computational methods to address population history in Africa (Patin et
al., 2009; Verdu et al., 2009). With the rapid accumulation of
multilocus genotype data and the significant increase in sampling
density, it is expected that similar inferential frameworks will be
successfully extended to explicit geographical modeling of human
dispersals within Africa.
Acknowledgements
This work was partially
financed by the research grants from Fundação para a
Ciência e a Tecnologia (FCT): PPCDT/BIA-BDE/56654/2004 and
PTDC/BIA-BDE/68999/2006.
References
Coelho M., Sequeira
F., Luiselli D., Beleza S. & Rocha J. 2009. On the edge of
Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic
variation in southwestern Angola. BMC Evol. Biol., 21; 9:80.
Coop
G., Pickrell J.K., Novembre J., Kudaravalli S., Li J. et al. 2009. The
role of geography in human adaptation. PLoS Genet., 5:e1000500.
Cruciani
F., Santolamazza P., Shen P., Macaulay V., Moral P., et al. 2002.
A back migration from Asia to sub-Saharan Africa is supported by
high-resolution analysis of human Y-chromosome haplotypes. Am. J. Hum.
Genet., 70: 1197-214.
Destro-Bisol
G., Donati F., Coia V., Boschi I., Verginelli F. et al. 2004. Variation
of female and male lineages in sub-Saharan populations: the importance
of sociocultural factors. Mol. Biol. Evol., 21:1673-82.
Patin
E., Laval G., Barreiro L.B., Salas A., Semino O., et al. 2009.
Inferring the demographic history of African farmers and pygmy
hunter-gatherers using a multilocus resequencing data set. PLoS Genet.,
4:e1000448.
Salas
A., Richards M., De la Fe T., Lareu M.V., Sobrino B., et al. 2002. The
making of the African mtDNA landscape. Am. J. Hum. Genet., 71:
1082-111.
Tishkoff
S.A., Reed F.A., Friedlaender F.R., Ehret C., Ranciaro A., et al.
2009. The genetic structure and history of Africans and African
Americans. Science., 22: 1035-44.
Verdu
P., Austerlitz F., Estoup A., Vitalis R., Georges M., et al. 2009.
Origins and genetic diversity of pygmy hunter-gatherers from Western
Central Africa. Curr. Biol. 19: 312-8. Epub 2009 Feb 5.
|
Jeroen PIJPE (The Netherlands)*
Skewed male population
substructure among an agriculturalist Ghanaian tribe
Socio-economic and cultural factors might play an important role in
explaining differences in human population genetic structure. To
explain patterns in population substructure, studies so far have
analyzed genetic differences among widely dispersed populations, and
did not consider differences among clans within the same tribe and/or
village. We conducted a detailed tribal specific micro-geographic study
to investigate the influence of socio-economic and anthropological
factors on population genetic structure. We analyzed the DNA of 205
males from the Bimoba tribe living in the single village of Farfar in
the Upper East Region of Ghana. These males belong to 6 different clans
and were living in 93 different compounds scattered over an area of
approximately 4 km2.
We found a striking, skewed male population substructure due to an
almost complete lack of male mediated gene flow among clans, as
reported by 15 Y-chromosomal Short Tandem Repeats (STRs) and a series
of biallelic Single Nucleotide Polymorphisms (SNPs) defining the Y-
chromosome haplogroup lineage E1b1a. We found a markedly skewed male
population substructure due to an almost complete lack of male gene
flow among clans of the Bimoba tribe within one single village. Males
were classified in Y-haplogroups E1b1a*, E1b1a7a* and E1b1a8*. In
contrast, data from mtDNA HVR-1 sequence, and from 15 autosomal STRs
indicate a virtually random female mediated gene flow among clans.
On the micro-geographic scale of a single village, population genetic
structure among a traditional agricultural people is deeply influenced
by the social structures. The Y-chromosome lineage is highly skewed by
clan(-group) membership, whereas female mediated gene flow is not bound
by such social structures. This pattern can be explained by the
patrilocal and patrilineal structure in such societies, and by past
migration events. The Bimoba offer a valuable insight into the cultural
processes that have shaped genetic variation in humans.
*With:
Tom van der Hulle, Hans J. Meij, Kristiaan van der Gaag, P. Eline
Slagboom, Rudi G.J. Westendorp, Peter de Knijff
|
|
Sergio TOFANELLI
(Italy)*
Malagasy admixture: the
tale of a recent encounter between deep-rooted lineages and beyond
We fit the history of Malagasy admixture in a highly resolved
phylo-genetic framework by typing a large set of uni-parentally
transmitted markers in unrelated individuals from inland and coastal
ethnic groups. The uniqueness of Malagasy was confirmed to be due to a
recent encounter between gene pools (Insular Southeast Asian and
sub-Saharan African) that have been shaped by at least 60,000 years of
independent evolution. The distribution of the two ancestral components
was ethnic and sex biased, with the Asian ancestry appearing more
conserved in the female than in the male gene pool and in inland than
in coastal groups. Thanks to forward simulations and the use of a novel
and more accurate measure of genetic distance (DHS), the focus about
the origin of Malagasy lineages was enlarged in space and pushed back
in time. Complex underlying demographies after the admixture event
could make the search of univocal ancestries inconclusive and the close
link between Malagasy and Bornean (Maanyan) vocabulary misleading. The
pattern of diffusion was compatible with a primary admixture of
proto-Malay people with Bantu speakers bearing a western-like pool of
haplotypes, followed by a secondary flow of Southeastern Bantu speakers
unpaired for gender and geography. Some groups appear suitable cases
for admixture mapping studies aimed at detecting disease-associated
variants that differ markedly in frequency between the two parental
populations
*With:
Stefania Bertoncini (Università di Pisa, Pisa, Italy), Loredana
Castrì
(Università di Bologna, Bologna, Italy), Donata Luiselli
(Università di
Bologna, Bologna, Italy), Francesc Calafell (Universitat Pompeu Fabra,
Barcelona, Spain), Giuseppe Donati (Oxford Brookes University, Oxford,
UK), Giorgio Paoli (Università di Pisa, Pisa, Italy)
|
|
Fulvio CRUCIANI
(Italy)*
Human Y-chromosome
haplogroup R1b1a (R-V88): A paternal genetic record of early-mid
Holocene trans-Saharan connections
Human Y chromosomes belonging to haplogroup R-P25 are quite rare in
Africa, being found mainly in Asia and Europe. However, a group of P25
Y chromosomes that are not defined by the presence of a downstream
derived marker (the paragroup R-P25*) are found concentrated in the
central-western part of the African continent, where they can be
detected at frequencies as high as 95%. Phylogenetic evidence and
coalescence time estimates suggest that R-P25* chromosomes (or their
phylogenetic ancestor) may have been carried to Africa by an
Asia-to-Africa back-migration in prehistoric times. Here we describe
six new mutations that define the relationships among the African
R-P25* Y chromosomes and between these African chromosomes and
previously reported R-P25 Eurasian sub-lineages. The incorporation of
these new mutations into a phylogeny of the R-P25 haplogroup led to the
identification of a new clade (R1b1a or R-V88) encompassing all the
African R-P25*, about half of the few European/west Asian R-P25*, and
the R-M18 chromosomes. A world-wide phylogeographic analysis of the
R-P25 haplogroup provided strong support to the Asia-to-Africa
back-migration hypothesis. The analysis of the distribution of the
R-V88 haplogroup in more than 1,800 males from 69 African populations,
revealed a striking genetic contiguity between the Chadic-speaking
peoples from the central Sahel and several other Afroasiatic speaking
groups from North Africa. The R-V88 coalescence time was estimated at
9,200-5,600 kya, in the early-mid Holocene. We suggest that R-V88 is a
paternal genetic record of the proposed mid-Holocene migration of
proto-Chadic Afroasiatic speakers through the Central Sahara into the
Lake Chad Basin.
* With:
Beniamino Trombetta (1), Daniele Sellitto (2), Andrea Massaia (1),
Giovanni Destro-Bisol (3), Elizabeth Watson (4) Eliane Beraud Colomb
(5), Jean-Michel Dugoujon (6), Pedro Moral (7), Rosaria Scozzari (1)
(1) Dipartimento di Genetica e Biologia Molecolare, Sapienza
Università
di Roma, Rome 00185, Italy; (2) Istituto di Biologia e Patologia
Molecolari, Consiglio Nazionale delle Ricerche, Rome 00185, Italy; (3)
Dipartimento di Biologia Animale e dell'Uomo, Sapienza
Università di
Roma, Rome 00185, Italy; (4) The Swedish Museum of Natural History,
Stockholm, Sweden; (5) Laboratoire d'Immunologie, Hôpital the
Sainte-Marguerite, Marseille, France; (6) Laboratoire
d'Anthropobiologie, FRE 2960, Centre National de la Recherche
Scientifique (CNRS) Université Paul Sabatier, Toulouse, France;
(7)
Departament of Biologia Animal, Universitat de Barcelona, Barcelona,
Spain.
|
|
A. RANCIARO (USA)
(1)*
The Genetic Basis of
Lactase Persistence in Africa
In most individuals, the ability to digest lactose, the sugar present
in milk, declines rapidly after weaning because of decreasing levels of
the enzyme lactase (encoded by the LCT gene) in the small intestine.
However, there are individuals who maintain the ability to digest milk
into adulthood due to a genetic adaptation in populations that have a
history of pastoralism. In order to identify variants associated with
the lactase persistence (LP) trait and to study the evolutionary
history of LP in Africa, we resequenced 1.7 kb of intron 9 and 3.3 kb
of intron 13 of the MCM6 gene (associated with LP in Europeans)
upstream of LCT, and 2.0 kb of the promoter region of the LCT gene.
A total of 973 individuals representing 77 different groups from Africa
(n=68), Asia (n=3), Middle Eastern (n=3) and Europe (n=3) were used in
this study.
We analyzed genotype/phenotype associations in 410 individuals for
which we measured lactase activity (Lactose Tolerant Test) and
identified three variants significant associated with the LP trait in
Africans (G/C-14010, T/G-13915, and C/G-13907). We also identify a
strong signature of recent positive selection in several East African
pastoralist groups. Levels of nucleotide diversity and tests of
neutrality were performed and the negative trend in Tajima's D test is
consistent with positive directional selection. Simulations were
performed to rule out the possibility of demographic effect.
Microsatellite haplotype analysis was also used to reconstruct the
origin and spread of the LP associated variants in Africa. Our results
indicate that mutations associated with LP arose independently in
African populations. Additionally, we find evidence for an East African
origin for the spread of pastoralism into South Africa.
*With:
A. Ranciaro1, J. Hirbo1,2, F. Reed3, M. Campbell1, H. Muntaser4, O.
Sabah5, G. Destro-Bisol6, Alain Froment7 , Maritha J. Kotze8 ,Thomas B.
Nyambo9, S. A. Tishkoff1,10
1) Dept Genetics, University of Pennsylvania,
Philadelphia, PA; 2) Dept. of Biology, University of Maryland, College
Park, MD; 3) Dept. of Evolutionary Ecology, Max Planck Institute for
Evolutionary Biology, Plön, Germany; 4) Inst. of Endemic Diseases,
University of Khartoum, Sudan; 5) KEMRI, Nairobi, Kenya; 6) Dipt.
Biologia Animale e dell'Uomo, Universita' "La Sapienza", Rome, Italy;
7) UMR 208, IRD-MNHN, Musee de l'Homme, Paris; 8) Dept of Pathology,
Faculty of Health Sciences, University of Stellenbosch, Tygerberg,
South Africa; 9) Dept. of Biochemistry, Muhimbili University of Health
and Allied Sciences(MUHAS), Dar es Salaam, Tanzania; 10) Department of
Genetic and Biology, University of Pennsylvania, Philadelphia, PA.
|
|
Sara PIACENTINI
(Italy)*
GSTM1 and GSTT1 gene
polymorphisms in European and African populations
Glutathione S-transferases (GSTs) are a superfamily of multifunctional
proteins with fundamental roles in cellular detoxification. GSTs have
been grouped into numerous classes; many of GST’s are polymorphic and
their polymorphism may contribute to promoting individual differences
in their response to xenobiotics. This study is focused on GSTT1 and
GSTM1 gene polymorphisms, both of particular interest as
anthropogenetic markers in studies on intra- and inter-population
variability. The frequencies of null genotypes obtained by PCR
multiplex in two population samples of European-origin and two
population samples of African-origin were compared with those from
other populations of different origin reported in the literature this
with the aim of contributing to the geography of these markers. On the
basis of the results obtained from the statistical analyses, it is
possible to distinguish three main clusters represented by population
samples of African or Asian or European origin respectively. Other
populations are randomly distributed outside these three main clusters,
perhaps because of the low sample sizes.
Data from PCR allele-specific technique highlighted the possible
presence of a SNP (rs11550605) in the third exon of the GSTT1
gene
that leads to a change of the aminoacidic residue in position 104
(T104P). In the present study this substitution was not found and the
studied population does not exhibit this mutation. The sequencing of a
480 bp fragment of the GSTT1 gene (fifth exon, fourth intron and a
short part of the fourth exon) in a sample of the Italian population
was performed to assess the presence of SNPs in the GSTT1 gene; the
sequences were then compared with the reference one. No nucleotide
substitution was highlighted, so confirming the data in the literature
indicating low frequencies of mutations and heterozigosity.
* With:
Renato Polimanti, Maria Fuciarelli. Department of Biology, University
of Rome “Tor Vergata”
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Sarah MARKS (UK)*
Molecular
characterization of low recombination genomic regions for
bio-anthropological studies: The peopling of Southern Africa
It is now generally accepted that modern humans originated in Africa.
In recent years there have been studies into the genetic variation of
current human populations in order to understand past population
movement around the world (Underhill et al 2001, Li et al 2008).
Southern African genetic history, however, has so far been
understudied, despite possibilities that this region might have played
a significant role in the origins of modern humans (McBrearty and
Stringer 2007). For this study, a total of 10 genomic regions have been
selected, all on different chromosomes, all characterised by reduced
recombination rate (<0.1cM/Mb, with many being <0.001cM/Mb). Each
region is unlinked to a coding region and contains a minimum of 2 Short
Tandem Repeats (STRs). These STRs have been combined in three STR
multiplex reactions. Analysis of these regions in samples from Southern
Africa will be used to address questions of interest about population
genetic history in this area: 1) What (if any) admixture is present
between Bantu-speaking populations and hunter-gatherer and pastoralist
Khoisan speakers; 2) Whether gene flow occurred between populations
that were already present in the area before the arrival of the Bantu
agriculturalists; 3) How the genetic diversity of Southern African
populations compares with that of other African populations, and thus
how it relates to the emergence of modern humans.
* With:
Cristian Capelli
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Valeria MONTANO (1)*
A genetic perspective on
the spread of Bantu communities
Every anthropologist working on sub-Saharan African populations is
supposed to have faced the Bantu expansion's big deal. Bantu is a
language family that is currently spoken in a wide part of sub-Saharan
Africa, longitudinally extended from Cameroon to Kenya until the
extreme South, excluding a part of South Africa, Botswana, Namibia and
all Madagascar. The most accepted hypothesis about Bantus' origin
was put forward by Joseph Greenberg, who located the first communities
in the Benue River Valley, across South-Eastern Nigeria and West
Cameroon (Greenberg, 1949). Starting from linguistic and historical
hypotheses, Molecular Anthropologists have analyzed the genetic
structure of Bantu communities and proposed that the present day
distribution of several lineages of Y-chromosome and mitochondrial DNA
(mtDNA) could be a result of the expansion of Bantu speaking
peoples. The present work focuses on the Bantu populations that are
supposed to be in genetic and cultural continuity with the first
ancient communities, between Nigeria and Cameroon and other Bantu
communities of Cameroon, Gabon and Congo. All these populations are
supposed to have been involved in the Western stream Bantu migration
(Vansina 1984; Beleza et al., 2005). Our aim is to gain insights
into the population dynamics underlying the expansion of Bantu
languages through the analysis of the classical uniparental inherit
genetic systems (Y-chromosome and mtDNA ). Seventeen populations have
been analyzed for 21 SNPs and 17 STRs of the Y-chromosome and for the
hypervariable region I of the mtDNA. The results show different signals
of structuration for the two genetic systems, opening an avenue
to test hypotheses about the spread of Bantu languages.
*With:
Marcari V.1, Anayale O.3, Ferri G.4, Comas D.2, Destro-Bisol G.1.
1 Dipartmento di Biologia Animale e dell'Uomo, Università di
Roma
"La Sapienza", Rome, Italy Istituto Italiano di Antropologia, Rome,
Italy
2 Unitat de Biologia Evolutiva, Department de Ciencies Experimentals i
de la Salut, Universitat "Pompeu Fabra", Barcelona, Spain
3 Department of Zoology, Ibadan University, Ibadan, Nigeria
4 Department of Diagnostic and Laboratory Service and Legal Medicine,
Section of Legal Medicine, University of Modena and Reggio Emilia, Italy
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Evelyne HEYER (France)*
Origins and Genetic
Diversity of Pygmy Hunter-Gatherers from Western Central Africa
Central Africa is currently peopled by numerous sedentary
agriculturalist populations neighbouring the largest group of
mobile hunter-gatherers: the Pygmies. Although
archeological remains attest Homo sapiens’ presence in the
Congo Basin since at least 30,000 years, the demographic
history of these groups, including divergence and
admixture, remains widely unknown. Moreover, it is still
debated whether common history or convergent adaptation to
forest environment resulted in the short stature characterizing
the pygmies.
We genotyped 604 individuals at 28 autosomal tetranucleotide
microsatellite loci in 12 non-pygmy and nine neighbouring pygmy
populations. We found a high level of genetic heterogeneity among
Western Central African pygmies, and evidence of heterogeneous levels
of asymmetrical gene-flow from non-pygmies to pygmies, consistent with
the variable sociocultural barriers against intermarriages. Using
approximate Bayesian computation methods, we compared several
historical scenarios. The most likely points toward a unique ancestral
pygmy population that diversified about 2,800 years ago, contemporarily
with the Neolithic expansion of non-pygmy agriculturalists.
Our results show that recent isolation, genetic drift and heterogeneous
admixture enabled a rapid and substantial genetic differentiation among
Western Central African pygmies. Such admixture pattern is consistent
with the various sociocultural behaviours related to intermarriages
between pygmies and non-pygmies.
* With:
Paul Verdu 1, Frederic Austerlitz 2, Arnaud Estoup
3, Renaud Vitalis 1,
Myriam Georges 1, Sylvain Théry 1, Alain Froment 1, Sylvie Le
Boumins 1,
Antoine Gessain 4, Jean-Marie Hombert 5, Lolke Van der Veen 5,
Lluis
Quintana-Murci 6, Serge Bahuchet 1.
1 Ecoanthropology and Ethnobiology UMR 5145, CNRS-MNHN-Univ. Paris7,
Musée de l'Homme, 75016 Paris;
2 Laboratoire Ecologie Systématique et Evolution, CNRS UMR
8079,Univ
Paris-Sud, Orsay, F-91405; AgroParisTech, Paris, F-75231; Orsay,
F-91405;
3 INRA, UMR CBGP (INRA / IRD / Cirad / Montpellier SupAgro),
Campusinternational de Baillarguet, CS 30016, F-34988
Montferrier-sur-Lez cedex, France.
4 Unité d'Epidémiologie et Physiopathologie des Virus
Oncogènes, Institut Pasteur, 75015 Paris, France;
5 UMR5596 Institut des Sciences de l'Homme, 69363 Lyon, France;
6 Human Evolutionary Genetics Unit, CNRS URA3012, Institut
Pasteur,75015 Paris, France.
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John NOVEMBRE (USA)
Maps and migrations:
Insights to the genetic structure of Europe from single nucleotide
polymorphism data and principal components analysis
Department of Ecology and Evolutionary Biology;
Interdepartmental Program in Bioinformatics; University of California -
Los Angeles
Due to ease of accessibility, patterns of genetic variation in samples
of European individuals have been some of the most carefully
characterized throughout the world and arguably across any
species. Despite the intensive attention given to these samples,
basic questions still remain unanswered regarding what the dominant
patterns are and what ancestral events explain them. Part
of the challenge has been due to how statistical methods have been
applied to emerging data sets. In particular, non-model based
methods, especially principal components analysis (PCA), have played an
important role in how genetic data from these samples have been
interpreted.
While PCA was first pioneered in the 1970s to summarize patterns in
allele frequencies among samples, a novel form of individual-based PCA
has recently become popular in human population genetics (e.g. Price et
al. 2006). This resurgence is mainly due to the fact that when
doing genome-wide association mapping for disease susceptibility loci,
PC coordinates can be used as covariates to control for population
stratification. Further, individual-based PCA has been argued to
be attractive because it does not presume pre-defined groups nor does
it assume a discrete set of ancestral populations.
To understand its behavior more concretely, several recent theoretical
studies have helped make clear how PCA behaves in different
settings. Key results are that: (1) Under models of discrete,
well-differentiated populations, PCA will identify easily definable
clusters. Notably, detecting such clusters behaves like a phase
transition whereby if the number of markers and number of individuals
are increased above a certain threshold, clusters suddenly become
detectable (Patterson et al. 2006). (2) Under models of
continuous, spatial population structure, the PCA coordinates for
individuals (or even populations) take the form of gradients (or more
complex sinusoidal functions) over geographic space, even if the total
population is at a demographic equilibrium. These results are
interesting from the stand-point of interdisciplinary studies as this
behavior of PCA have been essentially understood in some
sub-disciplines of science (e.g. meteorology, image analysis) for some
time, but their relevance was only recently noted within the population
genetics community (Novembre and Stephens 2008). (3) The expected
PCA coordinates for each individual in a sample can be derived from
average pair-wise coalescent times among individuals in the sample;
doing so reveals how PCA is dependent on relative sample-sizes and
connects PCA to coalescent theory (McVean 2009).
These theoretical insights help greatly with the interpretation of PCA
results from many recent large-scale single nucleotide polymorphism
(SNP) studies. For example, in a recent collaboration
between GlaxoSmithKline and academic scientists, several thousand
European individuals were sampled and genotyped using the Affymetrix
500K SNP genotyping platform (the POPRES project, Nelson et al. 2008,
Novembre et al. 2008). The results show a striking correspondence
between genetics and geography even at fine spatial scales.
Studies by other groups at both the same and finer spatial scales (e.g.
within Finland and Iceland, e.g. Lao et al. 2008, Sabatti et al. 2009)
also support this connection between genetics and geography (although
in some cases the influence of relative sample sizes or the presence of
outlier populations distorts the basic pattern).
One major question that remains from this initial round of SNP studies
is: How do putative European population isolates fit into the broader
context of European genetic diversity and what does it suggest about
the peopling of Europe? To address this question we merged SNP
data from putative isolates sampled as part of the Human Genome
Diversity Project (e.g. French Basques, Sardinians, Orcadians, and the
Adygei, Cann et al. 2002) with SNP data from the POPRES European
samples. We also merge in novel SNP data from the Sorbs, a
previously uncharacterized, Slavic-speaking putative isolate from
Eastern Germany. Our analysis of the Sorbs has been part of an
interdisciplinary collaboration with medical geneticists from the
University of Leipzig (Tonjes, Kovacs, and Stumvoll) as well as a
historian from UCLA (Patrick Geary).
A second major unanswered question regards how to interpret PCA.
While (Novembre and Stephens 2008) show gradients can arise in PCA even
under general conditions where spatial autocorrelation exists in data
(e.g. equilibrium stepping-stone models), if an expansion has recently
occurred, does the direction of the PC1 gradient indicate its
direction? Surprisingly, the direction of the gradient in PC1,
under many expansion parameter settings, does not align with the
expansion wave (Francois et al. 2009). To explain this phenomenon, we
must consider the "allele surfing" phenomenon that takes place during
the expansion of a population due to serial founder effects and the
spatial patterns that are left behind by "surfed" alleles.
In sum, PCA is subject to a variety of behaviors that are sometimes
easily misunderstood. Nonetheless, PCA can serve as a flexible
exploratory tool for visualizing major patterns of population structure
in a sample and for quality control (e.g. identifying outliers and
batch effects in genotyping assays). Ultimately though, methods
that are tailored to detect specific demographic signatures (e.g. the
decay of diversity with distance from an origin or patterns of allele
surfing) will be the most powerful way forward in illuminating the
peopling of Europe.
References:
Cann, H.M., de Toma, C., Cazes, L., Legrand, M.F.,
Morel, V., Piouffre, L., Bodmer, J., Bodmer, W.F., Bonne-Tamir, B.,
Cambon-Thomsen, A. et al. 2002. A human genome diversity cell line
panel. Science 296(5566): 261-262.
Francois, O., Currat, M., Ray, N., Han, E., Excoffier, L., and
Novembre, J. 2009. Principal component analysis under population
genetic models of range expansion and admixture. Under review.
Lao, O., Lu, T.T., Nothnagel, M., Junge, O., Freitag-Wolf, S., Caliebe,
A., Balascakova, M., Bertranpetit, J., Bindoff, L.A., Comas, D. et al.
2008. Correlation between genetic and geographic structure in Europe.
Curr Biol 18(16): 1241-1248.
McVean, G. 2009. A genealogical interpretation of principal components
analysis. PLoS Genet 5(10): e1000686.
Nelson, M.R., Bryc, K., King, K.S., Indap, A., Boyko, A.R., Novembre,
J., Briley, L.P., Maruyama, Y., Waterworth, D.M., Waeber, G. et al.
2008. The Population Reference Sample, POPRES: a resource for
population, disease, and pharmacological genetics research. Am J Hum
Genet 83(3): 347-358.
Novembre, J., Johnson, T., Bryc, K., Kutalik, Z., Boyko, A.R., Auton,
A., Indap, A., King, K.S., Bergmann, S., Nelson, M.R. et al. 2008.
Genes mirror geography within Europe. Nature 456(7218): 98-101.
Novembre, J. and Stephens, M. 2008. Interpreting principal component
analyses of spatial population genetic variation. Nat Genet 40(5):
646-649.
Patterson, N., Price, A.L., and Reich, D. 2006. Population structure
and eigenanalysis. PLoS Genet 2(12): e190.
Price, A.L., Patterson, N.J., Plenge, R.M., Weinblatt, M.E., Shadick,
N.A., and Reich, D. 2006. Principal components analysis corrects for
stratification in genome-wide association studies. Nat Genet 38(8):
904-909.
Sabatti, C., Service, S.K., Hartikainen, A.L., Pouta, A., Ripatti, S.,
Brodsky, J., Jones, C.G., Zaitlen, N.A., Varilo, T., Kaakinen, M. et
al. 2009. Genome-wide association analysis of metabolic traits in a
birth cohort from a founder population. Nat Genet 41(1): 35-46.
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Alessio BOATTINI
(Italy)*
The Genographic Project
in Italy: Y-chromosome preliminary results and perspectives
The Genographic Project is a five year genetic anthropology study
(concluding in 2011) aimed to explore the migratory history of the
human species by analysing around 100,000 DNA samples from 10,000
worldwide populations. Our research group is currently collaborating
with the Genographic Center for Western and Central Europe (principal
investigators: David Comas, Jaume Bertranpetit, Begona Martinez-Cruz)
in order to sample and unravel the genetic variability of the Italian
population(s).
A preliminary biodemographic analysis, based on around 80,000 surnames
from more than 15 millions Italian individuals, was performed in order
to design an accurate sampling strategy. The resulting sampling map
served as a template for the actual DNA sampling campaign, to which
collaborated actively local Blood Transfusion Centers. 28 sampling
points were selected and 1,250 samples collected (around 40 individuals
per sample). Informed consent and pedigree information up to the third
generation were obtained from each participant. The study includes only
those individuals whose four grandparents were born in the same
sampling area.
At present Y-chromosome typing is in progress: around 680 individuals
were typed for 80 SNPs and 19 STRs.
Preliminary results show that 34 haplogroups are represented in our
sample, only five of them exceeding the 5% of the total. R1b1b2
lineages are the most frequent, recurring in around one third of the
samples. Other most common haplogroups are G2a, I2a2, E1b1b1a and J2a.
Besides Y-chromosome typing completion, mtDNA variability will be
investigated by sequencing the HVS-I and analysing 22 biallelic markers.
These data will allow to explore the Italian genetic history and to
shed light on the most important historical events related to the
peopling of the country. In particular, lineage-specific investigations
will serve as a powerful tool to unravel the complicated regional
patterns characterising Italian history.
* WIth:
A. Boattini, D. Yang Yao, A. Useli, B. Martinez-Cruz, G. Ciani, D.
Comas, J. Bertranpetit, D. Luiselli, D. Pettener.
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Carla CALO' ( Italy)*
Analysis of Y-chromosome
polymorphisms in the linguistic isolate of Carloforte (Sardinia)
Carloforte is the only village located on the small island of San
Pietro, off the southwestern coast of Sardinia (Italy). San Pietro was
first populated in 1738 by emigrants coming from the island of Tabarka
(Tunisia) and originating from Pegli (Liguria, Italy).
For about 10 generations, those Genovese migrants had very little
contact with the mainland populations of both Tunisia and Sardinia,
maintaining a separate cultural as well as genetic identity. The
cultural aspect is evident in the Pegli dialect, which is still spoken
today, making the Carloforte population a linguistic isolate (Vona et
al., 1996). Earlier studies based on matrimonial structure, classical
genetic markers and incidence of a specific disease provided evidence
that Carloforte is a genetic isolate as well (Vona et al., 1996; Heath
et al., 2001). Carloforte is characterized by a remarkably high
endogamy rate (75.42%) and high percentage of consanguineous marriages
(6.62%, alfa=1.63x10-3). Interestingly, in Carloforte the highest
inbreeding values (Fit) were observed after 1850, due to a positive
shift towards consanguineous marriages.
In this paper we present further data on the genetic structure of the
Carloforte population by reporting on the distribution of 17 Y-STRs and
Y-haplogroups.
Individuals from Carloforte selected for the present study (N=43) were
proven descendants of the village founders. Moreover, the participants
were chosen for not having ancestors in common, at least up to the
grandparental generation. For comparison we selected a sample from
Sulcis Iglesiente (southern-western of Sardinia), the nearest region to
Carloforte.
Results on Y-chromosome (STRs and haplogroups) confirmed the genetic
peculiarity of Carloforte, that turned out to be genetically
differentiated from Sulcis Iglesiente. It is worth noting that
Carloforte population shares common haplotypes with the Peninsular
Italian population and not with Sulcis Iglesiente. Y-chromosome
analysis confirmed the cultural and genetic isolation of Carloforte.
*With:
Vona G., Ghiani M.E., Scudiero C.M., Mameli A., Robledo R., Corrias L.
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R. LELLI (Italy)*
The peopling of Southern
Italy: A maternal view
Since prehistoric times Southern Italy has been a cultural crossroads
of the Mediterranean basin. Genetic data on the peoples of Basilicata
and Calabria are scarce and, particularly, no records on mtDNA
variability have been published.
In this study 415 individuals from Souther Italy was analysed for mtDNA
in order to provide their classification into haplogroups.
Median-joining network analysis was applied to observe the
relationship between the major lineages of the Southern Italians.
Mitochondrial DNA haplotypes of populations from Apulia, Basilicata,
Calabria, Campania and Sicily are compared, using multivariate
analysis, with those of other Italian and Mediterranean populations, so
as to investigate their genetic relationships.
The haplogroup distribution in the Southern Italian samples falls
within the typical pattern of mtDNA variability of Western Eurasia. The
comparison with other Mediterranean countries showed a substantial
homogeneity of the area, which is probably related to the historic
contact through the Mediterranean Sea.
The bulk of the data demonstrated that Southern Italy shows the typical
mtDNA pattern of Mediterranean basin variability, even though it is
likely that Southern Italy was less affected by the effects of the LGM,
which reduced genetic diversity in Europe.
* With:
OTTONI, C., MARTINEZ-LABARGA, C., RICKARDS, O.
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Valentina COIA (Italy)
(1,2)*
Italian oriental Alps:
mtDNA variation in geographically and linguistically isolated
populations
As a results of ancient and complex peopling processes and the presence
of physical barriers, the alpine area provides unique opportunities for
anthropological and genetic studies of geographical and linguistic
isolation. In the framework of the projects "Biodiversity and history
of the populations from Trentino (BIOSTRE)" and "Isolating the
isolates. Case study 2: Eastern Alpine communities" (PRIN projects
2007-2009), we investigated the genetic structure of twelve populations
from the eastern alpine area, including four linguistically isolated
groups. Our database includes 550 individuals relative to Italian (Val
di Sole, Val di Non, Val di Fiemme, Valle di Primiero, Valle
dell'Adige, Valle Giudicarie and Valle del Fersina from Trentino and
Val Cadore from Veneto), German [(Altipiano di Luserna from Trentino,
Sauris (Province of Udine), Sappada (Province of Belluno)] and Ladin
speaking communities (Val di Fassa from Trentino).
In this contribution, We report on variation of the mitochondrial DNA
(sequencing of the hypervariable region 1 and typing of 17 SNPs) and
compare the results obtained with literature data for
neighbouring European populations.
Our first results show a substantial differentiation between the
linguistically isolated populations, more evident for the
german-speaking communities, and other populations in terms of intra
and inter-genetic diversity and genetic signatures of demographic
history. At the same time, we observed a worth noting heterogeneity
among the linguistically isolated populations, even despite a common
linguistic background (e.g. among Ladin groups from the Dolomites or
between Sappada and Sauris communities).
*With:
Cinzia Battaggia1, Vera Damiani1, Fabrizio Rufo1, Federica Crivellaro4,
Patrizia Parisi5, Federica Trombetta5, Ilaria Boschi5, Laura
Baldassarri5, Cristian Capelli3, Stefano Grimaldi2, Annaluisa Pedrotti2
and G. Destro-Biso1,6
1 Dipartimento di Biologia Animale e dell'Uomo, Università "La
Sapienza" di Roma, Italia
2 Dipartimento di Filosofia, Storia e Beni Culturali, Università
degli Studi di Trento, Italia
3 Department of Zoology, University of Oxford, OX1 3PS, UK, Oxford
4 Leverhulme Centre for Human Evolutionary Studies, University of
Cambridge, UK
5 Istituto di Medicina Legale e delle Assicurazioni, Università
Cattolica di Roma, Italia
6 Istituto Italiano di Antropologia, Roma, Italia
The research is supported by the "Provincia Autonoma
di Trento" (Post-doc PAT to V.C) the M.I.U.R (to G.D-B.) and the
Istituto Italiano di Antropologia (to G.D-B.).
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Maria LOPEZ-VALENZUELA
(Spain)*
Analysis of Y-chromosome
variation in Gypsies
Gypsies are one of the most interesting ethnic groups in Europe due to
their semi-nomadic life style and their uncertain origin. Despite the
lack a written history, it has been suggested that they originated in
the Indian subcontinent and they arrived to Europe in recent historical
times. During their diasporas, Gypsies groups split as they migrate
across Europe, although the extent of their endogamic costumes and
isolation is not known. In the present study, Gypsies from several
locations across Europe are compared to their neighbouring populations.
The analysis of a set of 19 Y-chromosome STRs (Short Tandem Repeats)
shows that Gypsies exhibit a different haplotype composition and
reduced genetic diversity compared to the European groups, suggesting a
bottleneck during the colonization of Europe. However, the Gypsy groups
show certain degree of genetic flow from European groups, our results
show that the extent of this flow is different from country to country
. An haplogroup prediction based on the Y-STR profiles reveals
the
high frequency of haplogroup H in the Gypsy groups. This haplogroup is
shared by many Gypsy groups and is almost restricted to the Indian
subcontinent. Our results are in accordance with previous studies that
suggest that Gypsies originated in India in recent times from a small
number of founders.
*With:
Begoña Martínez-Cruz and David Comas.
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Roberto
RODRIGUEZ-DIAZ (Spain)*
Distribution of Surnames
and Genetic Flow in a Rural Spanish Region: Genetic Structure
The study of isolated populations with a subsistence economy is of
special interest regarding biodemography. The reason is that the
conditions to which they have been subjected are similar to those
present in great part of the history of our species, thus the
conclusions drawn can be widely extrapolated. In this work two
techniques have been employed (SOM and Monmonier), of recent
application in this field, to study the genetic structure of a small
rural Spanish region: Fuentes Carrionas. It has its origins in the
information contained in the matrimonies contracted and the family
reconstructions between 1880 and 1979. The coefficients of
relationships (Hedrick) have been calculated among the populations (by
isonymy and progenitor-descendant matrix) and their relationship with
geographical distances (Mantel) has been studied. Later, using
Monmonier's algorithm the genetic barriers have been examined. Finally,
applying self-organised maps, the distribution of surnames has been
studied.
The analysis demonstrates that isonymy and genetic flow offer similar
results (p<0.01) and that geographical distance is significantly
related to both (p<0.01), thus it seems to be the principal factor
of isolation. Nonetheless, the genetic barriers show a region divided
in two.
The distribution of surnames presents an identical division, 29.56%
appear almost exclusively in the north-eastern half and 21.91% in the
south-west. Both techniques yield coherent and complementary results.
Their combined use allows a very detailed study, from which other
results arise, which, although geographical distance has been the most
determining factor, others of different nature exist (orographic and
socio-economic) which have marked the genetic structure of Fuentes
Carrionas.
*With:
María José Blanco-Villegas (University of Salamanca,
Spain)
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Ashot HARUTYUNYAN*
When genetics and history
clash: The origins of Hamshen Armenians
The Hamshenis are an isolated geographic group of Armenians with a
strong ethnic identity who, until the early decades of the twentieth
century, inhabited the Pontus area on the southern coast of the Black
Sea. Scholars hold different views concerning their origins. Broadly
there are three alternative regions of origin suggested: (a) eastern
Armenia (an area roughly covered by the present state of Armenia), (b)
western Armenia (an area that is now part of Turkey), and (c) Central
Asia; with ‘Armenia’, in this context, meaning the historical country
as it existed in antiquity. To establish whether data from the non
recombining portion of the Y chromosome would support one or another of
the suggestions, so far as paternal descent is concerned, we screened
Armenian males of Hamsheni descent for 12 biallelic and 6
microsatellite Y chromosome markers and compared them with previously
published data from populations representative of the three candidate
regions. DNA samples were collected in 82 residents of two villages
(Novomichailovskiy and Tenguinka) on the Black Sea coastal area of
Russia (Krasnodar region) who refer to themselves as Janik Hamshenis.
Most of the ancestors of the extant group moved to these villages in
1915 from their settlements in the region of Samsun (westward from
original area Hamshen). We found significant differences between the
Hamshenis and other groups and support for western Armenia as the most
likely region of origin. Specifically, the Hamshenis share their “modal
haplotype”, described as that encountered at the highest frequency
(15.9%), only with Western Armenians (2.8%), while this haplotype is
completely absent in other groups. The haplotype distribution and
pattern of genetic distances suggest a high degree of genetic isolation
for the Hamshenis consistent with their retention of a distinct dialect
of Armenian.
*With:
Mark Thomas, Ashot Margaryan, Neil Bradman and Levon Yepiskoposyan.
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Renato POLIMANTI
(Italy)*
GST polymorphism in the
Italian population: Anthropogenetic marker or marker of susceptibility?
Glutathione S-Transferases (GSTs) (EC 2.5.1.18) are a supergene family
of enzymes with roles in the cellular detoxification of a wide range of
exogenous and endogenous compounds. In humans, seven GST classes
encoding cytosolic enzymes have been described (Alpha, Mu, Pi, Sigma,
Theta, Zeta and Omega). Examples of allelic variation have been
identified in several of these classes. The distribution of
polymorphisms related to the cytosolic GSTs has been described in
different populations and there is a growing literature showing
associations between GST genotype and clinical outcome. In the present
study some cytosolic GST polymorphisms (GSTA1*-69C/T, GSTM1*0,
GSTP1*I105V, GSTO1*A140D, GSTO1*E155del, GSTO1*E208K, GSTO2*N142D and
GSTT1*0) were investigated in an Italian population sample.
GSTO1*E155del and GSTO1*E208K alleles were detected using the
Confronting Two-Pair Primers (CTPP) analysis and allele specific PCR
respectively, while the analyses of other genetic polymorphisms were
performed by PCR-RFLP method. The aim of this study is to clarify the
geography of these genetic markers and the relationship between GST
gene polymorphism, ethnicity and the prevalence of certain diseases.
The results obtained were compared to those found for other populations
in previous studies. The comparison showed two different situations:
For some polymorphisms the allele frequencies proved to have different
patterns among African, Asian and European populations, while for other
GST gene polymorphism the allele frequencies were not significantly
different among the populations considered. Analyzing the mortality and
the morbidity of diseases linked to GST gene polymorphisms we tried to
assess the possible selection effect of diseases on GST genetic
variability. In conclusion the final outcome of this research should
lead to a better understanding of interactions between genetic
variability and disease susceptibility.
* With:
Sara Piacentini and Maria Fuciarelli. Department of Biology, University
of Rome “Tor Vergata”.
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Andrea NOVELLETTO
(Italy)
Diet-driven dynamics of
NAT2 variants in dispersed human populations
Genetic variation at NAT2 has been long recognized
as the cause of differential ability to metabolize a wide variety of
drugs of therapeutic use. We explored the pattern of genetic variation
in 12 human populations that significantly extend the geographic range
and resolution of previous surveys, to test the hypothesis that
different dietary regimens and lifestyles may explain inter-population
differences in NAT2 variation.
The entire coding region was resequenced in 98 subjects and six
polymorphic positions were genotyped in 150 additional subjects. A
single previously undescribed variant was found (34T>C; 12Y>H).
Our results can be summarized and interpreted as follows: 1) the NAT2
coding region is poorly differentiated in the population samples
examined; 2) the major determinant of inter-population diversity are
the phenotypic proportions; 3) population dispersals were not
accompanied by a concomitant accumulation of molecular diversity; 4)
the data fit the distribution obtained for neutral alleles already
attaining polymorphic frequencies at the time of exit out of Africa.
Conversely, haplotype frequencies significantly differ across groups of
populations with different subsistence styles. The pool of fast
haplotypes show a strong decreasing trend in the order
hunter-gatherers/pastoralists/agriculturalist.
Based on previous biochemical evidence, we suggest the diminished
dietary availability of folates resulting from the nutritional shift,
as the possible cause of the fitness increase associated to haplotypes
carrying mutations that reduce enzymatic activity.
We then propose that the present NAT2 diversity in human populations is
the result of three distinct processes: i) presence of variation for
slow-causing sites in widely dispersed populations (possibly as neutral
variation) before major shifts to pastoralism and/or agriculture; ii)
independent emergence of selective advantage for multiple slow-causing
mutations in populations shifting from H-G to pastoralism/agriculture;
iii) further introgression of slow-causing variants into populations
anchored to H-G by later gene flow.
*With:
Francesca Luca, Giuseppina Bubba,
Massimo Basile, Radim Brdicka, Emmanuel Michalodimitrakis, Olga
Rickards, Galina Vershubsky, Lluis Quintana-Murci, Andrey I. Kozlov,
Andrea Novelletto
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Elena GIGLI (Italy)*
An improved PCR method
for endogenous DNA retrieval in contaminated Neanderthal samples based
on the use of blocking primers
Neandertal skeletal remains are usually contaminated with modern human
DNA derived from handling and washing of the specimens during
excavation. Despite the fact that the distinct Neandertal haplotypes
allow the design of specific primer pairs, for instance in most of the
mitochondrial DNA (mtDNA)hypervariable region 1 (HVR1), the human
contaminants can often outnumber the endogenous DNA, thus preventing a
successful retrieval of Neandertal sequences. We have developed a novel
PCR method,based on the use of blocking primers that preferentially
bind to modern human contaminant DNA andblock their amplification, and
greatly improve the efficiency of Neandertal DNA retrieval. We tested
themethod in four El Sidro´n Neandertal samples (two teeth and
two bone
fragments) with differentcontamination levels and taphonomic
conditions, and we have been able to significantly increase
theNeandertal yield from figures around 25.23% (5–69.6%) up to 90.18%
(75.3–100%).
*With:
Morten Rasmussen, Sergi Civit, Antonio Rosas, Marco de la Rasilla,
Javier Fortea, M. Thomas P. Gilbert, Eske Willerslev, Carles
Lalueza-Fox.
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|
A. ZAULI (Italy)*
HaPlone: A user-friendly
web-based application for the menagement of molecular anthropology data
The “BiBi – Biodiversity and Bioinformatics” project (University of
Bologna Strategic Projects) was aimed to collect and organize molecular
anthropology samples and data. One of the specific goals was “the
design, the implementation, the test and maintenance of a data base
useful for theoretical studies”.
To that end we developed HaPlone, a web-based application built on top
of the state-of-the-art Plone (http://plone.org) content management
system. The application allows to store, inspect, search and retrieve
data through the familiar interface of a standard web browser.
Data are stored in the "Subject" data structure, containing both
personal and molecular data, that can be inserted, inspected and edited
using a user-friendly interface. For each subject, the application
calculates on-the-fly the haplogroup, based on its tested UEPs, as well
as the most recent common ancestor for each sexual lineage, based on
the stored population.
The system also takes care of checking data consistency and flags the
user for potential errors, such as inconsistent or conflicting UEPs or
out-of-range STRs within a given subject.
Population subsets can be easily selected (by location, haplogroup,
sex, MRCA) using simple query forms, whose reports also provide basic
statistics and charts on the selected sets. Furthermore selected
subject data can be readily exported to CSV files for processing by
other applications such as spreadsheets or statistical packages.
By leveraging on Plone access-control features, the application can
handle selective access to stored data, allowing fine-grained control
on what it can be accessed by an anonymous vs an authenticated user, so
it can be used both for internal information sharing and data
dissemination simultaneously.
Currently the prototype handles only Y-chromosome molecular data (UEPs
and STRs), but work is planned to extend data handling to mtDNA data
too.
*With:
A. Boattini, A. Eusebi, M. Amico, I. Rossi, D. Luiselli, R. Casadio, D.
Pettener.
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Avshalom
ZOOSSMANN-DISKIN (Israel)
The origin of Eastern
European Jews revealed by autosomal and sex chromosomal polymorphisms
Objective: This study aims to establish the likely origin of Eastern
European Jews.
Methods: This is done by genetic distance analysis of autosomal markers
and haplotypes on the X and Y chromosomes.
Results: According to the autosomal polymorphisms the investigated
Jewish populations do not share a common origin, and Eastern European
Jews are closer to Italians in particular and to Europeans in general
than to the other Jewish populations. The similarity of Eastern
European Jews to Italians and Europeans is also supported by the X
chromosomal haplotypes. In contrast according to the Y-chromosomal
haplotypes Eastern European Jews are closest to the non-Jewish
populations of the Eastern Mediterranean. The autosomal genetic
distance matrix has a very high correlation (0.789) with geography,
whereas the X-chromosomal and Y-chromosomal matrices have only a
moderate correlation (0.375 and 0.425 respectively).
Conclusions: The close genetic resemblance to Italians accords with the
historical presumption that Ashkenazi Jews started their migrations
across Europe in Italy and with historical evidence that conversion to
Judaism was common in ancient Rome. The reasons for the discrepancy
between the results based on the autosomes and the X chromosome on the
one hand and the Y chromosome on the other are discussed.
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Luca PAGANI (UK)*
Characterization, through
re-sequencing, of genetic variants associated
with high altitude adaptation in North Caucasian ethnic groups
We are searching for signals of positive selection at candidate
genes
for high-altitude adaptation in North Caucasian highlanders using
Illumina indexed re-sequencing. A total of 55 unrelated Daghestani from
three ethnic groups settled in ancient villages located over 2,000
meters above sea level were selected as the study population. Caucasian
lowlanders (Adygei, n = 20), CEU( n = 20) and 1 chimpanzee were used as
controls. Archeological evidence suggests a long history (>10,000
years) of living at high altitudes, making the Daghestani populations
suitable for studies of adaptation to hypoxic stress, but possibly also
experiencing an unusual demographic history. In order to disentangle
selective and demographic effects, fifteen candidate genes involved in
oxygen metabolism (HIF1?; PHD1; PHD2; PHD3; VHL; EPO; EPOr; VEGF; EDN1;
NOS3; ACE; ?,?,?,?-globin) were re-sequenced together with 27
putatively neutral control regions chosen from those used in the
Hominid Project and the ENCODE3 Project.
The regions of interest were amplified by long-PCR, checked by gel
electrophoresis and those belonging to the same individual pooled and
purified using the QIAquick PCR Purification Kit. Each pooled sample
was indexed by adding an eight-nucleotide tag according to a protocol
developed at the WTSI , and sequenced using the Illumina GAII platform.
The resulting reads were sorted by their tags and then aligned to the
reference sequence. False positive and false negative SNP call rates
were measured and an optimal set of SNP calls established.
Among more than 1000 novel SNPs, we found non-synonymous variants
within the HIF1?, ACE, EPOr and NOS3 genes that could be considered as
candidates for hypoxia adaptation. SNP patterns in the neutral regions
are being used to investigate the demographic history of the
populations and the candidate targets of positive selection are being
scanned for signals of positive selection.
*With:
Qasim Ayub (The Wellcome Trust Sanger Institute); Daniel MacArthur (The
Wellcome Trust Sanger Institute);Yali Xue (The Wellcome Trust Sanger
Institute); Iwanka Kozarewa (The Wellcome Trust Sanger Institute);
Daniel Turner (The Wellcome Trust Sanger Institute);Sergio Tofanelli
(Università di Pisa, Pisa, Italy);Kazima Bulayeva (Vavilov
Institute,
Moscow, Russia); Kenneth Kidd (Yale University,Connecticut, USA);
Giorgio Paoli (Università di Pisa,); Chris Tyler-Smith (The
Wellcome
Trust Sanger Institute).
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Turi KING (UK)*
Genome-wide analysis of
coancestry among men sharing British surnames
Men who share uncommon British surnames frequently share
high-resolution Y chromosome haplotypes, providing unambiguous evidence
of common paternal ancestry within the last 700 years. We are using
whole-genome analysis to examine the degree of autosomal coancestry
among apparently unrelated men who share both a surname and a Y
haplotype. Such groups are interesting because they represent easliy
ascertained cohorts midway between the pedigree and the population, and
could have utility in genetic epidemiological studies.
We are currently analyzing 80 men bearing six surnames with associated
spelling variants, using the Affymetrix SNP 6.0 chip to type 906,600
SNPs, and the homozygosity haplotype method to search for shared
autosomal segments.
*With:
Mark Jobling.
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Daniel FALUSH (UK)*
A new statistical method
to infer population admixture events using genetic variation data
We present a novel statistical method that uses densely-spaced Single-
Nucleotide-Polymorphism (SNP) data to identify the major admixture
events occurring throughout a population's history. The model has
several advantages over leading available analytical approaches in this
area, such as principal-components-analysis and STRUCTURE. In
particular it can simultaneously (i) take advantage of the information
inherent in patterns of linkage disequilibrium, i.e. non-random
associations amongst neighbouring SNPs along a chromosome, (ii)
efficiently analyse hundreds of individuals at hundreds of thousands of
SNPs genome-wide, and (iii) allow for relatively straight-forward
interpretation and direct inference of key historical parameters, such
as the proportions and times of major admixture events. Using simulated
data matched to currently available human datasets, we show that our
model can identify and accurately date admixture events that have
occurred between 7 and 150 generations ago. As our technique exploits
the rich information in genetic data to infer details of a population's
admixture history, it marks a powerful complement to anthropological
research and can help to resolve a number of existing controversies. We
present results from applications of our model genome-wide 650K SNP
data for individuals from 53 world-wide populations of the Human Genome
Diversity Panel (Science 319, 1100-1104. The analysis identifies
several important admixture events, some of which are historically well
established (e.g. identification of recent European genetic influx into
the Maya Native American population), others that can be placed into a
clear historical context (e.g. an East Asian genetic influx into
several Central and South Asian populations dated precisely to the era
of the Mongol empire), and some that are to our knowledge novel (e.g.
admixture in the Cambodian population between a Central/South Asian
source and an East Asian source dated to around the period of the
Cambodian Empire). Plus bonus, unveiling of project X, also involving
Daniel Lawson.
*With:
Garrett Hellenthal and Simon Myers.
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|
Marco SAZZINI (Italy)*
Is Molecular Anthropology
ready for the Next-Generation Sequencing
Technologies revolution? A whole transcriptome sequencing case study
In recent years, a new generation of non-Sanger-based sequencing
technologies has succeeded in sequencing DNA in a massively parallel
fashion, enabling a huge reduction in the per-base sequencing cost.
This has brought genomics back from large genome centres into
laboratories of small academic consortia, making the attainment of that
comprehensive perspective more feasible also in the field of Molecular
Anthropology research. The potential to explore the full spectrum of
the human genome variability in an extremely more detailed way respect
to the study of common variants lauchend by the HapMap project is thus
imminent and will presumably establish new baselines for human
evolutionary and complex diseases studies.
Nevertheless, a whole-genome sequencing approach still results
prohibitively expensive due to the high sequence coverage required, as
well as the huge amount of data rapidly produced by these
next-generation sequencing technologies (NGSTs) has turned out to be an
outstanding analytical challenge, making bioinformatics expertise and
facilities essential. Several questions remain with regard to the speed
and ease of NGSTs assimilation into the mainstream of Molecular
Anthropology.
In the attempt to deal with such questions, we describe results from a
Whole-Transcriptome Shotgun Sequencing (RNA-Seq) case study in which 30
million 36 bp cDNA reads were generated from an individual sequenced by
means of the Illumina technology. The mapping of reads to the human
genome reference sequence led to the identification of more than 2,000
single nucleotide substitutions, as well as to the achievement of
exhaustive alternative splicing and gene expression profiles. A
comprehensive qualitative and quantitative picture of a human
transcriptome was thus drawn, demonstrating that NGSTs actually provide
new promising opportunities for deepen the knowledge of human genome
variation by simultaneously assaying a wide spectrum of genetic and
genomic features in a time and cost-efficient way.
* With:
Paolo Garagnani1, Alessio Boattini1, Ilaria Iacobucci2, Alberto
Ferrarini3, Enrico Giacomelli3, Luciano Xumerle4, Giovanni Malerba4,
Massimo Delledonne3, Giovanni Martinelli2, Donata Luiselli1.
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Roscoe STANYON
(Italy)*
Evolutionary Molecular
Cytogenetics provides aPictorial Legacy of Human
Origins and an Explicative Foundation for Contemporary Genomics
The evolution of the human genome is an integral part of our
understanding of human origins. Chromosome painting in over 50 species
of primates has allowed us to trace the origin of the human genome and
reconstruct the karyotype of long extinct ancestors. Recently, in situ
hybridization of about 900 BAC (Bacterial Artifical Chromosomes) in an
array of primate species allowed us to track the evolution of marker
order within each human chromosome. Classically, centromere position
was considered highly conserved but the BAC hybridizations revealed
that centromeres frequently shift their position forming Evolutionary
New Centromeres (ENCs). On the evolutionary line between macaques and
humans there are 14 ENCs. An evolutionary perspective can provide
compelling underlying explicative grounds for contemporary genomic
phenomena. Knowledge of ENCs provides an explanation for the clustering
of human clinical neocentromeres. Clinical neocentromeres cluster at
‘‘hotspots’’that frequently are sites of deactivated centromeres or
harbor ENCs in various primate species. Chromosome 14 and 15 in the
ancestral primate genome were a single syntenic chromosome. This
chromosome was fissioned in the ancestor of hominoids. The original
centromere was deactivated and two new centromere formed, one for
chromosome 14 and another for chromosome 15. Clinical neocentromere
cluster at the domain of the inactivated centromere at 15q25. The
cluster of clinical neocentromeres at 3q26 is the locus where a ENC
formed in New World primates. We recently reported on a clinical
neocentromere at chr6:26,407-26,491 kb, precisely where our ancestor
had a centromere which was deactivated in the human line after
divergence from lesser apes. The centromere jumped back to its original
position 17 million years ago. We can hypothesize that clinical
neocentromeres and evolutionary neocentromere are two faces of the same
coin, an example of Dobzansky’s dictum that “nothing in biology makes
sense except in the light of evolution.”
* With:
Francesca Bigoni, Department of Evolutionary Biology, Laboratory of
Anthropology, University of Florence.
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Vincenza COLONNA
(Italy)*
Detection of genetic
structure in isolated populations: effects of consanguinity, divergence
time and effective population size
Small human populations tend to diverge genetically
from source populations because of several factors (e.g., geographical,
social, religious, linguistic) resulting in reproductive isolation. In
isolates with small effective population sizes (Ne) at the founding
event, genetic drift can rapidly cause genetic differentiation from the
source population. Further, subdivision may increase inbreeding, and
significantly contribute to reduce the effective population size. Thus,
in the absence of migration, isolates can rapidly diverge from source
populations, even when they separated recently, and so genetic
clustering could be observed even in closely-related populations.
With this study we investigate the influence of the study design on the
extent of clustering in two cases:
In the first case, we considered the presence of familial groups in the
sample. We used genetic data from two isolated villages with a common
origin, presenting a high degree of structuring, and for which
extensive genealogical data are available. We analyzed structuring
after removing pairs of relatives (to variable degrees of relatedness)
in samples from the two villages. We observed that measures of
population structuring decreased with the removal of familial groups,
demonstrating that, indeed, observed genetic structuring is a
consequence of consanguinity. Further, we estimated the numbers of
markers and sample sizes required to observe this effect.
In the second case, we considered the effect of divergence time (t) and
Ne, assuming constant population size, in a more general case of an
isolate separating from a source population. We considered variable
lapses of time within a maximum of 50 generations, and we expected to
observe decreasing clustering with increasing Ne and decreasing t. This
expectation was confirmed in our simulated data. We provide
quantitative estimates of this effect, as a function of Ne, t, and of
the numbers of markers and individuals considered.
*With:
§RR Ferrucci, #M Ciullo, *G Barbujani
§Dipartimento di Biologia ed Evoluzione, Università di
Ferrara, Ferrara, Italy
#Istituto di Genetica e Biofisica "A. Buzzati-Traverso", CNR, Napoli,
Italy
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Francesc CALAFELL
(Spain)*
Recombination-based human
population genomics
Most inferences in human population genetics are based on the
non-recombining mtDNA and NRY, and a hurdle usually cited in relation
to autosomal and X-chromosome data is the action of recombination. We
have turned this argument around by studying human population diversity
using, recombination events as genetic markers. To infer past
recombination events, we have used a software called IRiS, which uses
the patterns of adjacent SNPs created due to linkage disequilibrium by
means of a combinatoric as well as statistic algorithm based on
pattern-switch recognition. In a preliminary run of the model, about
7Mb in the X chromosome were studied in the males of the 11 populations
of the HapMap3 database, and 5166 recombination events were located
both in terms of the position and of the haplotypes carrying the signal
of the past event. Presence/absence of a particular recombination event
was coded for each chromosome studied, and such a binary string was
termed a "recotype". We confirmed that our analysis correlated with
recombination rates inferred through methods based on linkage
disequilibrium and on sperm typing. We then analyzed recombination
events and recotypes with the same toolkit available for SNPs and
haplotypes. Individual ancestry and population substructure were
detectable with higher resolution when using recombination events as
markers rather than when using traditional allele frequencies. In
addition, recombination analysis revealed an exclusive component within
the African samples that could correspond to the trace of ancestral
hunter-gatherer African populations. The use of recombination events as
genetic markers opens the door not only for human population genetics
but also for a deeper understanding on how recombination shapes
genomes.
*With:
Marta Melé, Asif Javed, Laxmi Parida, Jaume Bertranpetit.
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Martin RICHARDS (UK)
Archaeogenetics and the
peopling of Asia
Global patterns of human genetic
diversity suggest that modern human variation is broadly (albeit
shallowly) structured at the continental level, with South Asia and
East Asia (and probably also Southeast Asia) forming genetic clusters
or domains distinct both from each other and from (Native) America,
Australasia, west Eurasia and sub-Saharan Africa. This has been shown
by analysing multiple autosomal microsatellites using the STRUCTURE
software (Rosenberg et al. 2006). However, evidence is accumulating,
especially from the non-recombining marker systems, mitochondrial DNA
(mtDNA) and the non-recombining part of the Y chromosome (NRY), that
this is the result of sequential colonisation and expansion from very
small founder groups who dispersed from an East African homeland within
the last 70,000 years (ky) or so (Macaulay et al. 2005; Metspalu 2006;
Richards et al. 2006).
Recent archaeological
and fossil evidence suggests that anatomically modern humans were
settled in Southeast Asia by at least 50 kya, implying that South Asia
was already settled by this time, although unequivocal evidence from
the Subcontinent is more recent. Genetic estimates are much less
precise, but a recent new calibration of the mtDNA mutation rate, which
employs the entire variation in the mtDNA genome for maximum precision
and makes allowance for the action of purifying selection, therefore
also maximising accuracy, provides at least one molecular clock that
can be employed for phylogeographic reconstructions (Soares et al.
2009). This suggests that Asia was first settled by modern humans 60-70
kya - somewhat earlier than the earliest widely accepted archaeological
evidence, but matching some evidence from Australia and perhaps also
China that is less widely accepted.
It was initially assumed
that Eurasia had been settled by modern humans via northeast Africa and
the Levant, ~50 kya, and Y-chromosome evidence has been used to argue
for a Central Asian "heartland" from which much of the Old World was
settled (Wells et al. 2001). However, the aforementioned dating
evidence from Australia suggested an earlier dispersal from the Horn of
Africa across the Red Sea and along the tropical southern Asian
coastline. This was supported by the extremely high number of basal
mtDNA haplogroup R and M lineages in India (Sun et al. 2006), and by
similarities between industries associated with modern humans in South
Africa ~60 kya and South Asia at least 35 kya (Mellars 2006).
Analysis of complete
mtDNA genomes sequences from so-called "relict" populations in South
Asia, Southeast Asia and Australasia have been used to address this
question. Modern non-African populations throughout the world, with the
exception of populations or regions with a recent African ancestry,
harbour mtDNAs from just three major founder clades, M, N and (nested
closely within N) R, all of which belong to the L3 clade, which is of
sub-Saharan African origin ~70 kya. Aboriginal populations in South
Asia, Southeast Asia and Australasia display mtDNA profiles that
include basal lineages belonging to all three of the mtDNA founder
clades, indicating that even the most ancient populations on the
southern coast of Asia were part of the same, single dispersal out of
Africa (Macaulay 2005).
This pattern, and the
molecular-clock timing of the dispersal to at least 60 kya, suggest
that the primary expansion was along the southern coastal route, with
the Asian continental heartland (including Southwest Asia, and
ultimately Europe) taking place subsequently along various corridors as
climatic conditions allowed, most likely after 50 kya. These dates seem
to exclude the possibility, suggested on archaeological grounds as well
as on earlier genetic analyses, that the dispersal into South and
Southeast Asia took place before the volcanic eruption of Toba in
Sumatra ~74 kya, which is therefore unlikely to have impacted on Asian
populations. Moreover, the dispersal seems to have been extremely
rapid, within the space of a few thousand years, since it led to the
divergence of the distinct domains of basal mtDNA lineages in each
region, rather than a pattern of nesting (such as occurred in the
settlement of the Americas from East Asia and the Remote Pacific from
Southeast Asia/Near Oceania).
There is relatively
little differentiation between ethnic and language groups within South
Asia, similar to other parts of Eurasia. The Indian Subcontinent has
long been seen as having been deeply affected by migrations from the
north, and the non-recombining markers and autosomal SNP analysis
indeed suggest genetic gradients, but these have arisen from a variety
of distinct prehistoric dispersals, with little or no impact
attributable to the putative Aryan migrations that are thought to have
led to the establishment of the caste system. There are mtDNAs in India
that originated in Southwest Asia but probably arrived not long from
the time of first settlement, and only a tiny minority that
appear to have arrived during historical times. The demic impact of the
Southwest Asian Neolithic appears to have been similarly minor for most
of the Subcontinent, despite some claims to the contrary (Chaubey et
al. 2006).
Southeast Asia was
settled by the southern coastal route by ~55 kya according to the mtDNA
clock, when much of Island Southeast Asia formed part of the mainland
as the Sunda continent. Dental patterns, as well as genetic diversity,
suggest that East Asia was initially settled from the south, although
there is a suggestion in Y-chromosome patterns of an early offshoot
from the southern route east of the Himalayas into the region of the
Tibetan plateau, sometime referred to as the "mammoth steppe". The
northeast Asian coast was reached at least 30 kya; some mtDNA and
Y-chromosome lineages in Japan appear to trace to this time. Genetic
and fossil data indicate discontinuities in the prehistory of East
Asia; there are suggestions of subsequent re-dispersals from south to
north, which may be in part due to Neolithic expansions, but seem
likely to also reflect the expansion of Han Chinese people within the
last 1500 years or so. The impact of the Last Glacial Maximum is also
likely to have been severe in continental East Asia, whereas refugial
areas existed within Southeast Asia. Sea-level rises beginning ~19 kya
had their maximal impact, however, in Southeast Asia; the Sunda
continent was inundated leading to wide scale dispersals of lineages
across what is now Island Southeast Asia which may have had a much
greater demographic impact than the subsequent Holocene spread of the
Neolithic across Southeast Asia and into the Pacific islands (Soares et
al. 2008).
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Soares, P., J. A.
Trejaut, J.-H. Loo, C. Hill, M. Mormina, C.-L. Lee, Y.-M. Chen, G.
Hudjashov, P. Forster, V. Macaulay, D. Bulbeck, S. Oppenheimer, M. Lin
and M. B. Richards. 2008. Climate change and post-glacial human
dispersals in Southeast Asia. Mol Biol. Evol. 25: 1209-1218.
Sun, C., Q.-P. Kong, M.
g. Palanichamy, S. Agrawal, H.-J. Bandelt, Y.-G. Yao, F. Khan, C.-L.
Zhu, T. K. Chaudhuri and Y.-P. Zhang. 2006. The dazzling array of basal
branches in the mtDNA macrohaplogroup M from India as inferred from
complete genomes. . Mol Biol. Evol. 23: 683-690.
Wells, R. S., N.
Yuldasheva, R. Ruzibakiev, P. A. Underhill, I. Evseeva, J. Blue-Smith,
L. Jin, B. Su, R. Pitchappan, S. Shanmugalakshmi, K. Balakrishnan, M.
Read, N. M. Pearson, l. T. Zerja, M. T. Webster, I. Zholoshvili, E.
Jamarjashvili, S. Gambarov, B. Nikbin, A. Dostiev, O. Aknazarov, P.
Zalloua, I. Tsoy, M. Kitaev, M. Mirrakhimov, A. Chariev and W. F.
Bodmer. 2001. The Eurasian heartland: a continental perspective on
Y-chromosome diversity. Proc. Natl Acad. Sci. USA 98: 10244-10249.
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Laure SEGUREL
(France)*
Looking for genetic
adaptations to diet from a comparative study of herders and
agriculturalists in Central Asia
During the vast majority of their past, humans have been
hunter-gatherers, with a diet poor in carbohydrates and a variable
availability of food. This dietary pattern could have led to strong
selective pressure for insulin resistance, a phenotype saving the
precious glucose. Nowadays, in industrialized conditions (a high
quantity and density of food with less physical activity), these past
adaptations might have became an important genetic burden, leading for
example to type II diabetes or other “civilization diseases”. However,
since the Neolithic transition, nearly 10.000 BCE, while
hunter-gatherers and herders would still need to select for insulin
resistance, farmers could have seen this selective constraint released,
thanks to high levels of carbohydrates in their new diet. According to
these hypothesis, i.e. the thrifty genotype (Neel, 1962) and the
carnivore connection (Colagiuri & Miller, 2002), past genetic
adaptations to lifestyle are therefore responsible of important health
disparities between ethnic groups. To test these hypotheses, we have
collected phenotypic and genetic data in Central Asia, for Tajiks and
Kyrgyz, known to be respectively long-term farmer and herder
populations. We have found that herders have nearly twice more risk to
be insulin resistant than farmers, which is consistent with the
previous evolutionary hypothesis. Furthermore, tests of neutrality on
11 candidate genes, known to be associated with type II diabetes, have
revealed signals of balancing and local selection on some genes, which
could therefore be involved in past adaptations to diet. However, for
these genes, the causative mutation has been found in higher frequency
in farmers. Further analyzes based on haplotypic data will certainly
help us to understand how strongly and when these selection events have
occured.
*With:
Patrick Pasquet, Myriam Georges, Tanya Hegay, Almaz Aldashev, Renaud
Vitalis & Evelyne Heyer.
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Frederick DELFIN*
Y-chromosome genetic
diversity of Filipino Negrito and non-Negrito groups
The Philippines are considered to be a strategic crossroad for
human
migrations in the Asia-Pacific region, and the origins and diversity of
Filipino groups have been popularly explained to be the result of
several migratory incursions of populations from neighboring geographic
regions. Of particular interest are Filipino Negritos, who with their
characteristic short stature, kinked hair, dark skin and traditional
hunter-gatherer mode of subsistence have been considered to be
descended from the earliest migration of modern humans to the
Philippines, which may also be the earliest migration to the
Asia-Pacific region. As such a historical distinction between Negrito
and non-Negrito Filipino groups has been perpetuated. Despite
considerable anthropological interest in these groups, there is a
paucity of genetic data on Filipino groups. We surveyed Y-chromosome
diversity in 16 Filipino language groups (including six Negrito groups)
and found extensive genetic diversity within, and heterogeneity among,
both Negrito and non-Negrito groups. We find no Y-chromosome genetic
support for the dichotomy between Negrito and non-Negrito groups.
Filipino groups appear to have diverse genetic affinities with
different populations in the Asia-Pacific region. Intriguingly, we find
genetic links between some Negrito groups and indigenous Australians
that may support the view that Negrito groups are descended from an
early migration of modern humans to the Asia-Pacific region.
* With:
Jazelyn M. Salvador, Gayvelline C. Calacal, Henry B. Perdigon,
Kristina A. Tabbada, Lilian P. Villamor, Saturnina C. Halos,
Ellen
Gunnarsdóttir, Sean Myles, David A. Hughes, Shuhua Xu, Li Jin,
Oscar
Lao, Manfred Kayser, Matthew E. Hurles, Mark Stoneking and Maria
Corazon A. De Ungria.
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Ellen Droefn
GUNNARSDOTTIR (Germany)*
High-throughput
sequencing of complete mtDNA genomes in three groups from the
Philippines
The Philippines is vastly rich in cultural and ethnic diversity; of 85
million inhabitants there are over 100 ethno-linguistic groups spread
over 7000 islands. All languages spoken in the Philippines today belong
to the Austronesian language family and it is believed that the
majority of the inhabitants are descended from Austronesian farmers who
migrated from Taiwan around 4000-6000 years ago. But old human fossils
dating as far back as 47,000 BP indicate that the Philippines were
settled much earlier than the Austronesian expansion. It has been
proposed that “Negrito” groups in the Philippines have a distinct
genetic origin because of their physical appearance (short stature,
dark skin color, frizzy hair). To support this hypothesis the
linguistic diversity of these Negrito groups accounts for a quarter of
all the linguistic diversity in the Philippines, even though they only
make up ~0.03% of the total population. However, little is known about
genetic diversity in Negrito and other ethno-linguistic Filipino
groups. Here we present 108 complete mtDNA genome sequences, generated
by high-throughput sequencing technology, from three groups from
Mindanao in the Philippines; Surigaonon, Manobo and Mamanwa (a Negrito
group). The data support the hypothesis that the Negritos represent an
early, separate migration to the Philippines, as they possess a unique
haplogroup, containing previously unreported mutations, that branches
off at the root of macrohaplogroup N. This study demonstrates the
advantages of high-throughput sequencing of complete mtDNA
genomes,
both by giving unbiased estimates of genetic diversity and by refining
the mitochondrial phylogenetic tree.
*With:
Mark Stoneking.
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Irina PUGACH (Germany)*
A genetic record of
Australian aborigines based on large-scale genotyping data
Australia holds some of the earliest archaeological evidence for the
expansion of modern humans out of Africa, with initial occupation of
Sahul (the Australia-New Guinea landmass) 40,000 to 60,000 years
ago.
Australia and New Guinea were separated by rising waters only during
the end of last glaciation 8,000 years ago, which, if this landmass was
settled by one population, amounts to around 40,000 years of shared
history for the Australians and New Guineans. Studies of mtDNA
and
Y-chromosome genetic variation reveal little or no association between
these two populations, and the nature of this dissimilarity is still
being debated. We are currently working with large-scale
genotyping
data from Australian aborigines, produced using the Affymetrix SNP
Array 6.0 platform. We have carried out principal component
analysis
on more than 750,000 autosomal SNPs, and our results suggest that the
ancient association between Australia and New Guinea does indeed exist,
but that these populations must have separated very early in the
history of Sahul. The extent of isolation of Australia
following
initial colonization is also a matter of debate; for example it has
been suggested that gene flow to Australia from the Indian subcontinent
occurred at the time of the introduction of dingo, and the appearance
of microliths, during the Holocene. Using a maximum-likelihood
based
software frappe, we were able to detect a signal which reflects
migration from India to Australia in times before European
contact.
Strikingly, we also detect a signal indicative of ancient shared
ancestry between Indian populations and Australia. It is
possible,
that this signal reflects the first human dispersal from Africa,
through India to Oceania. We are also looking for
haplotypes with
significantly longer than expected ranges of linkage disequilibrium
(LD) to identify genomic regions bearing signatures of local positive
selection.
* With:
Rostislav Matveyev, Kun Tang, David Lopez Herraez, Marc Bauchet, Peter
Nurnberg, Manfred Kayser and Mark Stoneking.
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Mannis VAN HOVEN
(The Netherlands)*
Unexpected island effects
at an extreme: human genetic diversity in Nias
The Indonesian island of Nias is located ~110 km west of North Sumatra.
Its ~600,000 inhabitants speak a unique (Austronesian) language and are
considered a separate ethnic group within Island Southeast Asia. To
investigate the genetic affinities of Nias islanders, we analyzed
paternally inherited Y chromosome (NRY) and maternally inherited
mitochondrial (mt)DNA markers in a representative sample of >400
individuals from accross the island. Surprisingly, basically only two
NRY haplogroups were observed, one predominantly in the north and the
other only in the south of the island. Nineteen mtDNA haplogroups were
observed, one of them being present at a frequency of 40% and all
others at frequencies below 10%. Both Y-chromosome short tandem repeat
(Y-STR) diversity and mtDNA hypervariable segment 1 (HVS1) diversity
were found to be highly reduced in Nias as compared to other regional
populations. Y-STR diversity was even lower than that of most
Polynesian islands where, unlike Nias, reduced diversity is expected
due to their remote geographic location. These observations suggest an
unexpected and previously undetected severe bottleneck in Nias’
population history and show that Nias forms an exception to the general
pattern of high genetic diversity in Island Southeast Asian populations.
* With:
Marja van Schoor, Johannes Hämmerle, Lea Brown, Ingo Kennerknecht,
Manfred Kayser.
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Connie MULLIGAN
(USA)*
A genetic perspective on
peopling of the Americas
* Connie J. Mulligan, Department of Anthropology,
University of Florida, Gainesville, FL 32605, USA
The colonization of the Americas represents the most recent major human
occupation of an uninhabited land mass on the planet. Therefore, we may
be able to ask increasingly specific questions and provide more
detailed information about this process than for other older and more
complicated processes such as the initial migration of anatomically
modern humans out of Africa. There are certain aspects of the
colonization that are agreed upon by the scientific community, i.e. a
single migration originated from an East Asian source and crossed over
the Bering land bridge before entering North America (summarized in
Fig. 1 and Kitchen et al. 2008). This process created a strong
population bottleneck such that modern Native Americans show
significant reductions in genetic variation relative to other global
populations and, furthermore, genetic variation throughout the Americas
shows evidence of substantial genetic drift. Less consensus has been
reached for other parameters of the colonization process such as the
timing of the migration (both leaving Asia and entering the Americas),
size of the founding population, nature of the migration from Asia
(continuous movement versus several short-range migrations), and
migration route(s) taken within the Americas.
Consensus on peopling of the Americas. An East Asian source population
for the Americas, most likely around the Lake Baikal region, is widely
accepted based on mtDNA and Y chromosome data. The idea of an early
European migration to the Americas prior to Columbus' voyage in the
1490s was once proposed based on presumed Caucasoid features of the
famous 'Kennewick Man' discovered in the state of Washington, but
support for this idea has largely disappeared based on comparative
skeletal analyses. The number of migrations was initially under debate,
but has converged on a single migration based on a wealth of data
including mitochondrial DNA (mtDNA), Y chromosome markers, short
nuclear DNA sequences, and autosomal microsatellite markers (Mulligan
et al. 2004, Wang et al. 2007, Fagundes et al. 2008) and most recently,
X chromosome sequence and nuclear single nucleotide polymorphism (SNP)
data (Bourgeois et al. 2009, Gutenkunst et al. 2009). Furthermore, most
geneticists believe there was virtually no ancient gene flow between
Asia and the Americas after the initial migration, likely reflecting
inundation of the exposed Bering land bridge after the last glacial
maximum (LGM) ~18,000-23,000 years ago.
Once humans entered the Americas, it appears that their movement may
have been very rapid based on archaeological evidence of human
occupation at Monte Verde at the southern extent of South America
~14,500 years ago (Dillehay 2008). Simple simulation studies show that
a rapid expansion is necessary to maintain frequencies of the major
mitochondrial haplogroups into the southern reaches of the Americas
(Fix 2004). Empirical and simulation data suggest that genetic drift
has played a significant role in determining patterns of Native
American genetic diversity as evidenced by greater differentiation and
population structure throughout the Americas relative to other
continents, reflecting the rapid dispersal, small population size, and
genetic isolation of Native American groups. Native American genetic
diversity also shows evidence of substantial admixture, particularly
through the incursion of European Y chromosomes (Wang et al. 2007).
Debated points on peopling of the Americas. Of the issues still under
active debate, the timing of the migration is a critical point. First,
it must be established that there are at least two relevant dates, the
migration out of Asia and the entry into the Americas. The first date
is generally based on the initial diversification of New World-specific
haplogroups. For example, mtDNA data support a date of ~30,000-40,000
years ago (Bonatto and Salzano 1997), reflecting the initial
diversification of New World genetic variation as the populations
diverged from ancestral Asians but prior to their entry to the New
World. The timing of entry to the Americas is more debated and dates
generally fall into periods that are pre- and post-LGM. Different dates
are frequently based on similar mtDNA datasets but use different
mitochondrial genome substitution rates, i.e. 'fast' substitution rates
(e.g. ~1.7 x 10-8 substitutions/site/year) support a post-LGM entry and
'slow' substitution rates (e.g. ~1.26 x 10-8 substitutions/site/year)
support a pre-LGM entry. Endicott and Ho (2008) recommend that
substitution rate estimates should be based on an 'internal
calibration' of the underlying phylogeny used in the rate estimation;
their estimates of the mitochondrial coding genome substitution rate
generally support younger dates, i.e. post-LGM entry.
The tempo of the migration has recently received widespread attention,
e.g. Tamm et al. 2007. This issue can be viewed as an investigation of
the movement of people (was it a continuous movement or a series of
short-range migrations?) or a focus on when (and where) did the genetic
variation that is specific to and ubiquitous throughout the New World
occur? There are mitochondrial variants that define New World-specific
haplogroups, e.g. C1b, C1d, X2a (Tamm et al. 2007) prompting
researchers to propose a period of population isolation prior to
expansion into the Americas (first mentioned by Bonatto and Salzano
1997). Mulligan et al. (2008) estimated that ~7000-15,000 years were
required to generate the New World-specific variation. It has been
further proposed that the migrating population occupied Beringia during
this period of isolation. Paleoecological data from ancient eastern
Beringia are indicative of productive, dry grassland suggesting that
Beringia was able to sustain at least small populations of humans and
other large mammals. The lack of archaeological data for human
occupation of Beringia most likely reflects the fact that the proposed
occupation sites are now inundated.
The size of the founding population has also been the subject of
considerable study. New estimates based on mtDNA coding genomes and
short nuclear sequences support an effective population size of
~1,000-2,000 individuals (Fagundes et al. 2007, Mulligan et al. 2008).
Once the population entered the Americas, there is considerable
interest in determining the exact route(s) taken by the migrants. The
distribution of two specific mtDNA haplogroups was used to support both
coastal and inland routes (Perego et al. 2009), but simulation and
empirical studies of whole mitochondrial genomes and hundreds of
autosomal microsatellite markers strongly support coastal routes over
inland routes (Fix 2004, Wang et al. 2007, Fagundes et al. 2008).
Future research. There are multiple aspects of the peopling of the
Americas that are still subject to debate and, thus, warrant attention.
1) Better estimates of substitution rates, both mitochondrial and
nuclear, are necessary to provide robust support for age estimates of
key events within the colonization process. This is particularly true
for estimates of entry to the Americas since a pre-LGM entry implies
that the migrant population overcame severe climatic and geologic, i.e.
North American ice sheets, obstacles to survive that would not have
been present if their entry postdated the LGM. 2) A better
understanding of the period prior to entry to the Americas is also
worthy of study, i.e. Was Beringia the occupied land mass? How long was
the occupation? What proportion of the population actually entered the
Americas? 3) Continued investigation of patterns of genetic variation
within the Americas is necessary in order to better understand the
various regional colonization events that occurred after the initial
entry to the Americas. Studies that look for correlation between
genetics and linguistics have a checkered history in terms of providing
general insights; most likely, correlation between linguistics and
genetics will reflect unique regional histories and not general trends
or processes during the course of colonization. 4) There is a move
towards more simulation of data and modeling of alternative
evolutionary scenarios in addition to continued collection of empirical
data. The simulation and modeling approaches have the advantage of
statistically determining the goodness of fit between empirical data
and alternative scenarios. For example, the support for a coastal and
inland route within the Americas was supported by the differential
distribution of two distinctive mitochondrial haplogroups (Perego et
al. 2009); it would be informative to know how often such a
distribution occurs by random chance and, thus, if the actual
distribution is sufficiently unique to require explanation via separate
migration routes within the Americas. 5) A broad perspective on the
colonization process is also valuable. Comparison with other
colonization processes, i.e. migration out of Africa, provides a
complementary perspective and allows general inferences on the
colonization process to be formulated.
References:
Bonatto S.L. & Salzano F. M. 1997.
Diversity and age of the four major mtDNA haplogroups, and their
implications for the peopling of the New World. Am. J. Hum. Genet.,
61:1413-1423.
Bourgeois S., Yotova V., Wang S., Bourtoumieu S., Moreau C., Michalski
R., et al., 2009. X-chromosome lineages and the settlement of the
Americas. Am. J. Phys. Anthropol. 140:417-428.
Dillehay T.D. 2008. Probing deeper into first American studies. Proc.
Natl. Acad. Sci. USA. 106:971-978.
Endicott P. & Ho S. 2008. A Bayesian evaluation of human
mitochondrial substitution rates. Am. J. Hum. Genet., 82:895-902.
Fagundes N.J.R., Ray N., Beaumont M., Neuenschwander S., Salzano F.M.,
Bonatto S.L., Excoffier L. 2007. Statistical evaluation of alternative
models of human evolution. Proc. Natl. Acad. Sci. USA, 104(45):17614-9.
Fagundes N.J.R., Kanitz R., Eckert R., Valls A.C.S., Bogo M.R., Salzano
F.M., et al. 2008. Mitochondrial population genomics supports a single
pre-Clovis origin with a coastal route for the peopling of the
Americas. Am. J. Hum. Genet. 82:583-592.
Fix A.G. 2004. Rapid deployment of the five founding Amerind mtNDA
haplogroups via coastal and riverine colonization. Am. J. Phys.
Anthropol. 128:430-436.
Gutenkunst R.N., Hernandez R.D., Williamson S.H., Bustamante C.D. 2009.
Inferring the joint demographic history of multiple populations from
multidimensional SNP frequency data. PLoS Genetics, 5:e1000695.
Kitchen D., Miyamoto M.M., Mulligan C.J. 2008. A three-stage
colonization model for the peopling of the Americas, PLoS ONE,
2(9):e1596.
Mulligan C.J., Kitchen A., Miyamoto M.M. 2008. Updated three-stage
model for the peopling of the Americas. PLoS ONE, 3(9):e3199.
Mulligan C.J., Hunley K., Cole S., Long J.C. 2004. Population genetics,
history, and health patterns in native Americans. Annu. Rev. Genom.
Hum. Genet. 5:295-315.
Perego U.A., Achilli A., Angerhofer N., Accetturo M., Pala M., Olivieri
A., et al. 2009. Distinctive Paleo-Indian migration routes from
Beringia marked by two rare mtDNA haplogroups. Curr. Biol. 19:1-8.
Tamm E., Kivisild T., Reidla M., Metspalu M., Smith D.G.,
Mulligan C.J., et al. 2007. Beringian standstill and spread of Native
American founders. PLoS ONE, e829.
Wang S., Lewis C.M., Jakobsson M., Ramachandran S., Ray N., Bedoya G.,
et al., (2007) Genetic variation and population structure in Native
Americans. PLoS Genet. 3:e185.
Figure
1. Maps depicting a three-step colonization model for the peopling of
the Americas. (A) Divergence, then gradual population expansion of the
Amerind ancestors from an East Central Asian gene pool (blue arrow).
(B) Proto-Amerind occupation of Beringia with little to no population
growth for "15,000 years. (C) Rapid colonization of the New World by a
founder group migrating southward through the ice free, inland corridor
between the eastern Laurentide and western Cordilleran Ice Sheets
(green arrow) and/or along the Pacific coast (red arrow). A scaled-down
version of Beringia today (60% reduction of A-C) is presented in the
lower left corner. Modified from Kitchen et al. 2008.
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Rebecca JUST (USA)*
Characterization of a
Native American mtDNA haplogroup C lineage
A new mtDNA haplogroup C founder lineage (“C4c”) was recently
identified in two Native Americans from Colombia [1]. The aim of
the
present study was to generate additional entire mitochondrial genome
sequences to further characterize this clade.
An American mtDNA control region population database was searched for
potential C4 lineages (i.e. any haplogroup C sequence not attributable
to C1 or C5). Entire mtDNA sequences were generated for a subset
of
the samples identified and from five private donors (n=21). A C4
phylogenetic tree incorporating both the newly generated and published
entire mtDNA genome sequences was constructed and considered in
comparison to recently published phylogenies [1-3].
We propose a revised definition of C4 in which previous Asian clades
C4a and C4b are re-designated C4a1 and C4a2, and which now also
includes former branch C7 [2,4]. Fourteen of the newly generated
sequences and the previously published Colombian genome cluster
together and comprise a Native American clade we term C4a3.
Coalescent
times estimated for the C4a and C4a3 nodes are in agreement with
previously published estimates for the divergence of Native American
and Asian lineages [4]. The inclusion of two new Native American
sequences within the Asian C4a1 clade may indicate additional
haplogroup C4 American founders. These data refine the poorly
characterized Native American C4a3 founder lineage and modify the
haplogroup C phylogeny.
[1] Tamm et al. Beringian standstill and
spread of Native American founders. PLoS One 2007; 9:e829.
[2] Volodko et al. Mitochondrial genome diversity in Arctic Siberians,
with particular reference to the evolutionary history of Beringia and
the Pleistocenic Peopling of the Americas. Am J Hum Genet 2008;
82:1084-1100.
[3] van Oven and Kayser. Updated comprehensive phylogenetic tree of
global human mitochondrial DNA variation. Hum Mutat 30(2):e386-E394.
http://www.phylotree.org.
[4] Soares et al. Correcting for purifying selection: an improved
mitochondrial molecular clock. Am J Hum Genet 2009; 84:740–759.
*With:
Josefina M.B. Motti, Erin M. Gorden, Jodi A. Irwin, Jessica L. Saunier,
Melissa K. Scheible, Michael D. Coble, Claudio M. Bravi.
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Sidia Maria
CALLEGARI-JACQUES (Brazil)*
Autosomal STR
polymorphisms and population structure in Native Amazonian groups
Amazonia was an entrance door for the first colonizers of South
America, and humans have being there for at least 12 thousand years. At
present, almost half of the 350,000 Brazilian Natives live in the area.
Despite several decades of genetic studies performed with these groups,
a clear understanding of the population structure in Native Amazonians
is lacking. Various degrees of interpopulation diversity have been
found, which were explained by possible barriers produced by the Amazon
river or linguistic differences. However, the evidence was not strong
and was based on classical genetic systems not as variable as the
molecular markers. As part of our efforts to understand human Amazonian
variability, we studied eleven short tandem repeat loci (CSF1P0,
D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11,
TH01, and TPOX) in 11 Native groups (526 individuals). The aim was to
test for major geographic or linguistic barriers to gene flow and,
possibly, to find an anthropological or ethnological explanation for
the observed patterns. We found high inter-Native population variation,
the lowest values of average heterozygosity and number of alleles being
observed in four isolated tribes that had contact with non-Native
populations in recent times (1921-1989). Analysis of Molecular
Variance, Generalized Hierarchical Modeling, and the STRUCTURE Bayesian
analysis indicated no significant geographical or linguistic barriers
to gene flow. But, we observed that genetic similarity decreases
according to linear geographic distances bound to 300 km, suggesting
that the genetic structure of Native Amazonian group may be better
explained by an isolation-by-distance model.
* With:
Sidney E. B. dos Santos, Elzemar M. Ribeiro-Rodrigues, Ândrea K.
C. Ribeiro-dos-Santos, Mara H. Hutz, Luciana Tovo-Rodrigues, and
Francisco M. Salzano.
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Mark WHITTEN (1)
(Germany)
Investigating potential
ascertainment bias in sample selection using
complete mitochondrial DNA genome sequences of Siberian populations
Previous research on mtDNA HVR1 sequences from Siberian populations
(Sakha (Yakut), Tuvan, Even, Evenk, and Yukaghir) has uncovered a high
percentage of sequence type sharing, thus making it difficult to detect
putative admixture. Sequencing complete mtDNA genomes allows for more
fine-scaled analyses to be performed which should provide a better
understanding of the history of these populations.
Traditionally, complete mtDNA sequences have been generated using
Sanger sequencing methods. However, presumably because of the increased
costs and time involved with sequencing all samples in a collection,
the majority of the complete mtDNA genomes deposited in GenBank either
come from studies focusing on specific haplogroups of interest or from
studies where only samples with unique mtDNA HVR1 sequences were chosen
for complete mtDNA sequencing. An underlying assumption of the latter
selection process is that if HVR1 sequences are identical between
individuals then their complete mtDNA genomes should also be identical.
However, if this assumption is incorrect, an ascertainment bias is
potentially introduced.
To investigate this possible bias, we sequenced the complete mtDNA
genomes of nearly 400 Siberian samples using a novel protocol that
combines the preparation of indexed libraries from genomic DNA with
hybridization enrichment of mtDNA for sequencing on the Illumina Genome
Analyzer II. This is a rapid, cost-effective method for sequencing
complete mtDNA genomes to high coverage (~50-fold).
We examined whether selecting samples for complete mtDNA sequencing
based on HVR1 identity excludes potentially informative polymorphic
sites and found that only around one-third of the pairs of individuals
with identical HVR1 sequences also have identical complete mtDNA
genomes. Currently, we are determining the extent to which this biased
sampling affects analyses of Siberian population prehistory. The higher
resolution achieved with complete sequences is expected to shed light
on the degree of admixture between groups whose languages show signs of
intimate contact.
*With:
MINGKUN LI (2), CESARE DE FILIPPO (1), BRIGITTE PAKENDORF (1)
1. Junior Scientists Group on Comparative Population Linguistics, Max
Planck Institute for Evolutionary Anthropology, 2. Department of
Evolutionary Genetics, Max Planck Institute for Evolutionary
Anthropology.
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Lutz ROEWER (Germany)*
Local evolution in the
Amazon basin - studies of Y chromosome markers
The tribal population under study, the Waorani, live in the Amazonian
region in the east of Ecuador. The Waorani have a forest-dwelling
hunter-gathering lifestyle, specific cultural practices and distinctive
physical traits, e.g. a low mean stature. While Waorani groups with
6-10 families traditionally practised a nomadic lifestyle moving
regularly from one camp to another, the current way of life is becoming
sedentary. The aim of our study was twofold. First we study whether
traditional family and clan system partially survived or broke down
under the influence of acculturation and admixture with neighbouring
ethnic groups and Western lifestyle. We compared two completely
different communities, one with a size of ~80 inhabitants living
according to their traditions and one school village with ~400 people
of mixed ethnic ancestry which have abandoned their culture and family
structures to a large extent. Altogether swabs of 154 individuals of
these two settlements were collected with group informed consent and
analysed for known Y chromosome markers. Secondly we addressed the
question of demographic history of the Waorani. For this purpose we
compared the polymorphisms found in this isolated population with
indigenous populations of the Amazon basin and other parts of South
America as collected in the YHRD 3.0 repository.
*With:
Geppert M, Willuweit S, Zweynert S, Baeta M, Nunez C,
Martínez-Jarreta B, Vacas-Cruz O, González-Solorzano J,
González-Andrade F
|
|
David COMAS (Spain)
The Genographic
Project: insights into Western/Central European variation
Institut de Biologia Evolutiva
(UPF-CSIC), CEXS-UPF-PRBB, Barcelona
The spread of Homo
sapiens out of Africa and the subsequent continent colonisations and
migrations have been reconstructed through the analyses of data
reported by several disciplines, such as paleoanthropology,
archaeology, linguistics and genetics. The joint effort of these
disciplines has allowed having a broad knowledge about the tempo and
mode of the origin of our species and the major colonisations at a
continental level. However, some migration routes, especially those
within continents, are far for been completely understood. In order to
shed light to the reconstruction of human migrations, National
Geographic and IBM, with the participation of the Waitt Family
Foundation, have launched the Genographic Project. This international
project aims to provide genetic data in order to reconstruct human
movements through the analysis of uniparental genomes (mitochondrial
DNA and Y chromosome). Several groups, one in each continent, are
collecting samples and performing the proper analyses. Within
Western/Central Europe, we are proceeding with the sample collection
and the first analyses of the results. These analyses will allow us to
provide a finer resolution of the migrations within Europe and
neighbouring geographic areas.
|
|
Guido BARBUJANI
(Italy)*
Inference of demographic
processes from comparisons of ancient and modern DNAs
* Dept. Biology
and Evolution, University of Ferrara
Our ability to infer past demographic changes has substantially
improved with the development of methods for the reliable typing of DNA
from ancient specimens. However, the inferential process remains
complicated, because ancient samples are small and the genetic
information they yield is generally limited to one marker, mtDNA.
Therefore, whenever dealing with ancient DNA evidence, besides asking
what is the demographic model best accounting for the observed patterns
in the data, one has also to consider whether there is enough
statistical power in the data to discriminate among alternative
models. To address the main question, one basically compares
scenarios of genetic continuity between ancient and modern samples with
scenarios in which the samples belong to different branches of the
genealogical tree.
Computer simulation of explicit demographic models is an effective
means to test hypotheses on the relationships between ancient and
modern samples. Serial coalescent approaches, in particular (Anderson
et al. 2005), allow one to generate genealogies from the present back
to the common ancestor, in which individuals are added at various
moments in time, representing modern and ancient samples. By
attributing a DNA sequence to the common ancestor of the whole
genealogy, and by randomly distibuting mutations on the genealogical
tree, one thus generates many simulated datasets. The sequences
themselves are arbitrary (in fact, strings of 0s and 1s), but their
differences are not, as they reflect the consequences of the
genealogical and of the mutational processes. Therefore, one can
estimate from them summary statistics, describing how genetic variation
would be if the model is true.
Algorithms of Approximate Bayesian Computations (ABC: Beaumont et al.
2002) allow comparisons among models, as well as the estimation of the
relevant demographic parameters. In short, genetic diversity in the
data is summarized by a number of observed summary statistics. Millions
of realizations of the demographic process assumed under each model are
generated by Serial coalescent simulation, with parameters sampled from
appropriately broad distributions of priors. An arbitrary number
(threshold) of simulation experiments showing the shortest Euclidean
distance between observed and simulated summary statistics are then
retained, and the model parameters are estimated from them. By counting
how often each specific model generated data falling within the
best-fitting simulation replicates, one estimates a global posterior
probability for each model. Algorithms exist for testing whether the
parameters estimated under each model depart significantly from the
observed statistics, and whether there is enough power in the data to
discriminate among models.
Two applications of this method to ancient DNA data from populations of
pre-classical Italy, are giving rather different desctiptions of the
evolution of genetic diversity through a time-bracket of some 2,500
years. In Sardinia, two modern populations separated in space by just
120 km, Ogliastra and Gallura, showed very different relationships with
a sample of 23 individuals from Bronze-age burials. A direct
genealogical continuity between Bronze-age Sardinians and the current
people of Ogliastra (a genetic isolate), but not Gallura, showed a much
higher probability than any alternative scenarios, regardless of the
method chosen for comparing models (Table 1). Also, there was evidence
that genetic diversity in Gallura evolved largely independently, owing
in part to gene flow from mainland Italy (Ghirotto et al. 2009).
In Tuscany, we are currently investigating the demographic scenarios
accounting for the observed relationships amnong modern and ancient
(Etruscan) inhabitants of the area. The Etruscans' biological origins
are unclear, with ancient historians suggesting either that they
immigrated from Anatolia, or alternatively that they represent an
autochtonous populations (Barker and Rasmussen, 1998); equally obscure
are their genealogical relationships with current inhabitants of
Tuscany. We had available a set of 20 Etruscan sequences (Vernesi et
al. 2004). In general, moderns Tuscans sampled in the areas of highest
density of Etruscan sites show some mtDNA resemblance with people of
the Eastern Mediterranean shore (Achilli et al. 2007), but not with the
Etruscans, and that difference is unlikely to result from systematic
errors in the ancient DNA sequences (Mateiu and Rannala, 2008).
In a preliminary ABC analysis of several modern and ancient samples,
the latter comprising Etruscans and Middle-age people from Tuscany
(Guimaraes et al. 2009), we compared three basic models of the
genealogical relationships among samples (Figure 1). We found no
evidence of genealogical continuity for two Tuscan communities, Murlo
and Volterra, for which Model 2 was clearly supported by data. On the
contrary, Model 1 received strong statistical support when we compared
with the ancient samples a third Tuscan area, Casentino. In addition,
we could fit model 1 also to the mtDNA sequences from a population of
the Western coast of Anatolia, where Herodotus placed the putative
origin of the Etruscans. To make sure that those findings had a
biological meaning, we also compared the Etruscans with other modern
Italian samples, finding again no evidence of genealogical continuity.
The apparent common ancestry does not clearly imply that modern Western
Anatolians and Casentino people are both descended from the Etruscans,
but rather that they share common ancestors who did not differ much
from the Etruscans. Herodotus proposed an origin of the Etruscan
culture in a migration episode from Anatolia less than 3000 years ago.
To test whether genetic data give any support to this interpretation,
we are currently estimating by IM methods the likely time of separation
of the two modern samples.
In general, the comparisons of ancient and modern DNA suggest that
genetic traces of the ancient inhabitants of a region can be found
among the modern people, but modern populations are a mosaic of mtDNAs,
and cannot be regarded as globally descended from the people who
inhabited the same regions in preclassical times.
References:
Achilli A., et al. (2007) Mitochondrial DNA
variation of
modern Tuscans supports the Near Eastern origin of Etruscans. American
Journal of Human Genetics 80: 759-768
Anderson, C.N., Ramakrishnan, U., Chan, Y.L. & Hadly, E.A. (2005)
Serial SimCoal: a population genetics model for data from multiple
populations and points in time. Bioinformatics 21: 1733-1734
Barker, G. & Rasmussen, T. (1998) The Etruscans. Blackwell, Oxford.
Beaumont, M.A., Zhang, W. & Balding, D.J. (2002) Approximate
Bayesian computation in population genetics. Genetics. 162: 2025-2035
Ghirotto S., Mona S., Benazzo A., Paparazzo F., Caramelli D., Barbujani
G. (2009) Inferring genealogical processes from patterns of Bronze-age
and modern DNA variation in Sardinia. Molecular Biology and Evolution
00: 000-000
Guimaraes, S. et al. (2009) Genealogical discontinuities among
Etruscan, Medieval and contemporary Tuscans. Molecular Biology and
Evolution 26: 2157-2166
Mateiu, L.M. & Rannala, B.H. (2008) Bayesian inference of errors in
ancient DNA caused by postmortem degradation. Molecular Biology and
Evolution 25: 1503-1511
Vernesi C., et al. (2004). The Etruscans: A population-genetic study.
American Journal of Human Genetics 74: 694-704
Table1. Posterior
probabilities of three models (detailed in the first row of the table)
of the genealogical relationships between ancient and modern
populations of Sardinia.
LR is the logistic regression method, AR is the
acceptance-rejection method, and threshold is the number of
best-fitting simulations considered for the comparison. For each method
and threshold (i.e., for each row of the table), the sum of posterior
probabilities is 1.
|
Method
|
Threshold
|
Model 1
(Ogliastra in
genealogical continuity with ancient Sardinians)
|
Model 2
(Gallura in
genealogical continuity with ancient Sardinia
|
Model 3
(Ogliastra and
Gallura in genealogical continuity with ancient Sardinians)
|
|
LR
|
50,000
|
0.956
|
0.018
|
0.027
|
|
LR
|
22,500
|
0.957
|
0.020
|
0.023
|
|
LR
|
12,000
|
0.961
|
0.019
|
0.021
|
|
LR
|
6,000
|
0.970
|
0.012
|
0.018
|
|
AR
|
500
|
0.760
|
0.120
|
0.120
|
|
AR
|
100
|
0.860
|
0.090
|
0.050
|
|
|
Claudio FRANCESCHI
(Italy) (1)*
Genetics and anthropology of aging,
age-related diseases and chaga's disease: the experience of the Bologna
group
Complex traits are difficult to disentangle, as the
phenotypes result from the interaction of different basic components
where genetics interacts with environment, epigenetics and
stochasticity (Cevenini et al., 2008). Studies in humans represent a
particular challenge, owing to the pervasive and profound influence of
cultural habits and specific evolutionary history on the different
human populations. We will discuss the importance of adopting an
integrated and multidisciplinary approach in genetic studies on two
complex traits, such as aging and Chagas disease, as the most
appropriate and correct methodology of data collection and
analysis.
Longevity
Longevity is a very complex trait (Leroi et al, 2005; Kirkwood et al.,
2005), and the phenotype of long-living people is not easy to define
(Passarino et al., 2007) The genetics of longevity has peculiar
and unexpected characteristics such as allele timing (Bonafè et
al., 2004; Invidia et al., 2009) increased homozygosity at several loci
(Bonafè et al., 2001a; Cardelli et al., 2008) gender prevalence
(Passarino et al., 2002) and specificity (Bonafè et al., 2001b)
, strong dependence on the demographic structure (Yashin et al., 1999;
Passarino et al., 2002; Cardelli et al., 2008) and epidemiological
specificities of the different populations, likely resulting from its
post-reproductive occurrence (De Benedictis & Franceschi,
2006), which in turn suggests a minor or negligible role of
natural selection. Thus, the genetics of longevity can be highly
population-specific, requires a large numer of subjects (Lescai et al.,
2009a) and different results in different populations are not
unexpected and cannot be taken, at first glance, as a simple lack of
reproducibility and validation failure (Cellini et al., 2005). The data
so far collected indicate that a variety of genes are involved
(Franceschi et al., 2005; Franceschi et al., 2007a; Salvioli et al.,
2006; Capri et al., 2008) but it interesting to note that those
involved in major pathways and functions such as IGF1/insulin pathway
(Bonafè et al., 2003), inflammation and immune responses
(Carrieri et al., 2004; Franceschi et al., 2005), oxidative stress and
lipid metabolism (Salvioli et al., 2005; Lescai et al., 2009b) and
sirtuins (Bellizzi et al., 2005) are well represented. Thus the
genetics of longevity requires ad hoc study design which are not easy
to perform in different populations (Franceschi et al., 2007; De Rango
et al., 2008)
We will report our experience regarding two studies which have peculiar
and unique characteristics, i.e.:
1. The AKEA study of
exceptional longevity in Sardinia (Deiana et al., 1999). In
order to identify the centenarians all over the island and to
collect data (health status, genealogical data) and biological samples
(blood) a complex logistical organization was set up. We will
review some of the major data we have collected regarding the
prevalence of centenarians and their sex ratio and geographical
clustering, as well as their phenotype and genotype (Passarino et
al., 2001; Deiana et al., 2002; Carru et al., 2003; Lio et al., 2003;
Poulain et al., 2004; Pes et al., 2004; Caselli et al., 2006; Polidori
et al., 2007, Scola et al., 2008).
2. The GEHA (GEnetics of
Healthy Aging) Project (2004-2010) in Europe (Franceschi et al.,
2007b). The aim of the project is to identify genes and gene
variants involved in human longevity and healthy aging, with particular
attention to the cross-talk between the nuclear and the mitochondrial
genomes. To this aim, within the framework of this European Union (EU)
project, 2500 old sibpairs (both sibs being 90+) and the same number of
sex- and ethnicity-matched younger controls have been recruited in 11
European countries. The genome wide linkage analysis on the 90+
sibpairs has been completed and a GWAS study in the oldest members of
the 90+ sibpairs is in progress. Moreover, mtDNA haplogroups and
sub-haplogroups have been analysed in all the recruited people, in
order to confirm in a large sample of subjects derived from different
geographical areas previous results suggesting a correlation between
human longevity and mtDNA variants, both germ-line inherited and
somatically acquired (De Benedictis et al, 1999; Zhang et al., 2003;
Rose et al., 2007), which appears to be population-specific (Dato et
al., 2004). Indeed, such studies on mtDNA variants at the population
level may be biased by a variety of methodological issues (Santoro et
al., 2006; Raule et al., 2007; Salvioli et al., 2008
).
In both studies, even if at a different scale, major logistical,
ethical and genetical problems related to the complexity of the
populations involved, emerged, stressing the necessity of a more
comprehensive and integrative approach, capable of including
demographers and historical demographers, anthropologists and
local historians, besides geneticists, population geneticists and
biogerontologists, for the best and more correct interpretation of the
genetic results
Chagas disease
Chagas disease affects several millions individuals in South
America, where the Trypanosoma cruzi is endemic and causes higher
mortality than any other parasite. Its main vector is the
haematophagous Triatoma infestans. Clinical manifestations range from
asymptomatic infections to potentially fatal cardiopathy. Rural
populations are the most affected, due to housing conditions and
underlying poverty and low education. Recently, cases of infected
subjects have been reported in USA and Europe as a result of the
massive migration from South America, arising problems for blood
donors, organ transplantations and new births. The aim of our study was
to test the hypothesis of a different genetic susceptibility to
the Trypanosoma cruzi infection and its clinical outcomes, in two
populations, such as the Wichi´ (Amerindian natives) and the
Criollos (a complex admixture of people of European and native origin),
living in the same geographic region of Argentinian Gran Chaco (Mission
Nueva Pompeya) where the infection is endemic (about 60-70% in both
populations), but having with different cultural habits and lifestyles
as well as different historical-genetic-demographic
characteristics. A critical issue in such field studies is represented
by the cultural and anthropological mismatch between the native
populations and the researchers coming from outside. Indeed, the
anthropologists working since several years with the Wichì and
Criollos in Mission Nueva Pompeya were fully aware that the
conceptualization of diseases and particularly that regarding Chagas
disease was substantially different from the one adopted by the
geneticists and medical doctors. To this regard, we would like to
stress the critical importance of the strict collaboration between the
anthropologists, the medical doctors and the population geneticists
which allowed us to overcome the non trivial and usually neglected
difficulties (cultural and logistical) related to the approval of the
Ethical Committees in Bologna and in Argentina, the
signature of the informed consent and the collection of biological
samples. Indeed, this study has been possible owing to the full
involvement of the native populations and the reciprocal respect
between the Wichì and Criollos and the anthropologists,
resulting from their previous careful field studies. It is worth
mentioning that the anthropologists devoted a particular
attention to the preparation of a bilingual (Wichì and
Spanish) booklets aiming to explain to the two communities the
characteristics of the Chagas disease as well the implications of their
participation to the study, taking into account their cultural
characteristics.
Within this scenario, a preliminary step was to assess the genetic
admixture of the populations under study, taking into account
cultural/anthropological and socio/economical variables. To this aim a
total of 600 individuals from the two populations was analysed With two
sets of uniparental markers (mtDNA and Y chromosome) in order to
estimate the degree of admixture and parental contributions in both
populations (Yang Yao et al., 2009). We characterised 17 STRs loci and
16 SNPs for the Y chromosome and the mtDNA haplogroups by sequencing
the entire Control Region (D-loop) followed by RFLP analysis of the
coding region. The Y chromosome SNPs definition shows a typical,
but very high, prevalence of Amerindian haplogroups in Wichi, while in
Criollos almost the same percentage represents European (admix analyses
highlight the main role of Spain and Italy) and Amerindian
contribution. The mtDNA haplogroup analysis revealed an Amerindian
origin for both populations, with the presence of European haplogroups
only in <2% of Criollos. These results shed lights on the extreme
admixture of the analysed populations and may help in explaining the
distribution of Chagas morbidity in the Gran Chaco region. In addition,
we are assessing the patterns of seropositivity in specific familiar
groups in relation to their different ethnic origin (Wichi` and
Criollos), and are studying polymorphisms of candidate autosomal genes,
to unravel the genetic basis of Chagas susceptibility.
Acknowledgements
The GEHA study is an Integrated Project funded by EU, FP6; the
investigations on Chagas's disease have been funded by the Consorzio
Interuniversitario Italiano per l'Argentina (CUIA), progetti 2006 e
2007.
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phenotypes. Biogerontology 8:283-90.
Pes G.M., Lio D., Carru C., Deiana L., Baggio G., Franceschi C.,
Ferrucci L., Oliveri F., Scola L., Crivello A., Candore G.,
Colonna-Romano G. & Caruso C. 2004. Association between longevity
and cytokine gene polymorphisms. A study in Sardinian centenarians.
Aging Clin. Exp. Res. 16:244-8.
Polidori M.C., Mariani E., Baggio G., Deiana L., Carru C., Pes G.M.,
Cecchetti R., Franceschi C., Senin U & Mecocci P. 2007. Different
antioxidant profiles in Italian centenarians: the Sardinia peculiarity.
Eur. J. Clin. Nutr. 61:922-4.
Poulain M, Pes GM, Grasland C, Carru C, Ferrucci L, Baggio G,
Franceschi C & Deiana L. 2004. Identification of a geographic
area characterized by extreme longevity in the Sardinia island: the
AKEA study. Exp Gerontol. 39: 1423-9
Raule N., Sevini F., Santoro A., Altilia S. & Franceschi C.. 2007.
Association studies on human mitochondrial DNA: methodological aspects
and results in the most common age-related diseases. Mitochondrion
7:29-38.
Rose G., Passarino G., Scornaienchi V., Romeo G., Dato S., Bellizzi D.,
Mari V., Feraco E., Maletta R., Bruni A., Franceschi C. & De
Benedictis G. 2007. The mitochondrial DNA control region shows
genetically correlated levels of heteroplasmy in leukocytes of
centenarians and their offspring. BMC Genomics. 8:293.
Salvioli S., Olivieri F., Marchegiani F., Cardelli M., Santoro A.,
Bellavista E., Mishto M., Invidia L., Capri M., Valensin S., Sevini F.,
Cevenini E., Celani L., Lescai F., Gonos E., Caruso C., Paolisso
G., De Benedictis G., Monti D. & Franceschi C. 2006. Genes, ageing
and longevity in humans: problems, advantages and perspectives. Free
Radic Res. 40:1303-23.
Salvioli S, Capri M, Santoro A, Raule N, Sevini F, Lukas S, Lanzarini
C, Monti D, Passarino G, Rose G, De Benedictis G & Franceschi C.
2008. The impact of mitochondrial DNA on human lifespan: a view from
studies on centenarians. Biotechnol. J. 3:740-9.
Santoro A., Salvioli S., Raule N., Capri M., Sevini F., Valensin S.,
Monti D., Bellizzi D., Passarino G., Rose G., De Benedictis G. &
Franceschi C. 2006. Mitochondrial DNA involvement in human longevity.
Biochim Biophys Acta. 1757:1388-99.
Scola L., Lio D., Candore G., Forte G.I., Colonna-Romano G., Pes M.G.,
Carru C., Ferrucci L., Deiana L., Baggio G., Franceschi C. & Caruso
C. 2008. Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian
centenarians. Exp Gerontol. 43:114-8
Yang Yao D., Luiselli D., Pettener D., Franceschi C., Sevini F., Raule
N., Barbieri A., Lomartire L., Santoro A., Teymoor K., Ferri G.,
Alu`M., Franceschi Z., Ciannameo A., Dasso M.C., Perez de la Hoz R.,
Moretti E., Basso B. & Castro I.. 2009. An anthropological-genetic
approach to Chagas disease in Gran Chaco (Argentina). Tropical
Med Intern Health suppl 2;14: 177
Yashin A.I., De Benedictis G., Vaupel J.W., Tan Q., Andreev K.F.,
Iachine I.A., Bonafe M., DeLuca M., Valensin S., Carotenuto L.
& Franceschi C. 1999. Genes, demography, and life span: the
contribution of demographic data in genetic studies on aging and
longevity. Am J Hum Genet. 65:1178-93.
Zhang J., Asin-Cayuela J., Fish J., Michikawa Y., Bonafe M., Olivieri
F., Passarino G., De Benedictis G., Franceschi C. & Attardi G.
2003. Strikingly higher frequency in centenarians and twins of mtDNA
mutation causing remodeling of replication origin in leukocytes. Proc
Natl Acad Sci U S A. 100:1116-21.
*With:
Daniele Yang Yao2, Federica Sevini1, Aurelia Santoro1, Donata
Luiselli2, Davide Pettener2, G. Ferri3, Maria Cristina Dasso4,
Riccardo Perez de la Hoz5, Edgardo Moretti6, Beatriz Basso6, Irma
Castro6, Anna Ciannameo7 and Zelda Franceschi7
1 Department of Experimental
Pathology,
2 Department of Experimental and Evolutionary Biology, University of
Bologna, Italy; Department of Forensic Medicine,
3 University of Modena and Reggio Emilia,
4 CIAFIC, Buenos Aires, Argentina,
5 Centro Universitario Interdisciplinario para el estudio de la
enfermedad del Chagas, UBA Universidad de Buenos Aires,
6 Servicio Nacional de Chagas and Universidad Nacional de Cordoba,
Cordoba, Argentina, 7Department of Historical Disciplines, University
of Bologna, Italy.
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Mark COLLARD (Canada)
Anthropology and
Archaeology
"Given the recent convergence of evolutionary
psychology and human behavioral ecology-sociobiology, one might expect
that the next generation of researchers will rapidly untangle all the
major mysteries of human behavior and cognition. Unfortunately, I do
not think that this will happen quickly. The main reason is that no
branch of the evolutionary social sciences has an adequate
understanding of human culture."
Kim Hill in The Evolution of Mind: Fundamental
Questions and Controversies, ed. by S.W. Gangestad and J.A. Simpson
(Guilford Press, 2007), p. 351.
Kim Hill's assessment of the state of "evolutionary culture studies" in
the foregoing quotation is overly pessimistic. For many years it was
certainly the case that attempts to develop an evolutionary approach to
human culture were not only few and far between, but also largely
theoretical. However, over the last 10 years the situation has changed,
and there is now a reasonably substantial body of empirical work in
which cultural data are analyzed within the framework of evolutionary
theory. This development should be of particular interest to molecular
anthropologists because it has been driven in large part by the use of
techniques developed by molecular biologists and other evolutionary
biologists. In this paper, I will review two of the main "threads"
within this body of work. One is the application of population genetic
modeling to cultural data. Most of the studies that form this thread
have employed the neutral model, but recently researchers have also
begun to use selection-based population genetic models. The other
thread I will discuss is the application of the cladistic method of
phylogenetic reconstruction to cultural data. The studies in which this
approach has been adopted have addressed a range of issues from the
processes that give rise to population-level cultural diversity to the
colonization of the New World to the evolution of ancient weapons
systems. In the final part of my talk I will outline some of the
problems that will have to be overcome before the evolutionary analysis
of culture becomes mainstream and suggest ways in which molecular
anthropologists can help.
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Quentin ATKINSON
(UK)*
The prospects for tracing
deep language ancestry
*
Institute of Cognitive and Evolutionary Anthropology, University of
Oxford, 64 Banbury Road, Oxford OX2 6PN, UNITED KINGDOM
"If we possessed a perfect pedigree
of mankind, a genealogical arrangement of the races of man would afford
the best classification of the various languages now spoken throughout
the world; and if all extinct languages, and all intermediate and
slowly changing dialects, had to be included, such an arrangement
would, I think, be the only possible one."
- The Origin
of Species, Charles Darwin (1859)
Whilst there is now broad agreement that our genetic
ancestry can be traced back to a late Pleistocene origin in Africa,
there is no such consensus about the roots of the world's 6000 or so
languages. Proposed language super-families - such as Amerind in the
Americas and Nostratic and Eurasiatic in Eurasia - or global language
classifications like those controversially linked to the human genetic
tree (Cavalli-Sforza et al., 1988), are viewed with scepticism by most
linguists. Words are thought to evolve too rapidly to allow reliable
identification of common ancestry beyond a limit of ~8ky BP (Ringe,
1998) and when apparent 'long-range' relationships are identified,
proponents have been unable to provide statistical verification that
any resemblances are beyond what would be expected by chance (Ringe,
1998). However, recent advances in the available data and methods (Dunn
et al., 2005; Pagel, 2000; Pagel et al., 2007; Reesink et al., In
press) suggest the established ~8ky limit may need to be re-evaluated
(Gray, 2005), potentially greatly extending the time depth over which
language ancestry is informative about human prehistory.
Most claims for long-range language relationships rest on putative
lexical homologues or 'cognates' identified on the basis of form and
meaning correspondences across languages. One reason many have found
this evidence hard to swallow is that the rate of replacement of
cognates through time appears to be too rapid and too unpredictable to
leave any reliable signal after just a few thousand years. For example,
Morris Swadesh's (Swadesh, 1952) early attempts to derive a single
lexical retention rate found that even among a set of 200 relatively
stable basic vocabulary terms, on average roughly 20% of cognates are
lost every 1000 years. As shown in Figure 1 (blue line), such a rate
implies that a pair of languages that diverged just 4,500 years ago
(separated by 9,000 years of change) is expected to share only five
cognates from an initial 200 in the Swadesh list. After 7,000 years,
this number drops below one. Under this scenario, proposals for
language classifications stretching back to the early Neolithic and
beyond seem completely untenable - the number of cognates at such time
depths will be too few to allow genuine historical signal to be
distinguished from chance resemblances.
However, not all words are created equal - some evolve more slowly than
others. Pagel (2000) has shown that a model of lexical evolution that
allows rates of change to differ across meanings fits the observed
distribution of lexical divergence in Indo-European better than
Swadesh's constant rate model. More recent work has revealed that the
rate at which different Swadesh list meanings evolve is correlated
across language families (Pagel & Meade 2006) and that the
frequency with which a meaning is used in everyday speech, together
with its part of speech, can explain almost 50% of the variation in
rates of lexical replacement (Pagel et al., 2007). Thus, commonly used
pronouns (such as I, you and we) and numerals (one, two, four and five)
evolve roughly 100 times slower than the rarer, more rapidly evolving
Swadesh adjectives and verbs (such as dirty, or to throw)(Pagel et al.,
2007). This predictable variation in rates of lexical replacement
dramatically increases the feasibility of reconstructing deep language
ancestry.
Figure 1 (red line) shows the expected number of surviving cognates
shared between language pairs for a given separation time based on the
empirically derived rate distribution from Pagel et al. (2007). Whilst
under a constant rate model it would take only 4,500 years to reduce
the cognate pool from 200 to five, allowing for rate variation extends
this threshold beyond 20,000 years. Even languages that separated
50kya, perhaps contemporaneous with the African exodus, are expected to
share at least two cognates. Of course, even if cognates exist at such
time depths, there remains the problem of identifying them and
demonstrating that any similarities are beyond what would be expected
by chance, but the predictability of rates across meanings may help
here too. Based on information about word frequency, part of speech or
rates of change within language families, one can predict not just how
many cognates should be shared between a pair of languages given some
time of separation, but which meanings are more likely to produce
cognate forms. Finding cognate forms for two or three meanings from a
possible 200 may not constitute convincing evidence for a relationship,
but if those meanings are also a priori expected to be the most stable,
then a case for common ancestry can be made.
As well as words, structural features of language, such as the set of
phonemes a language uses, its gender system or favoured word order, can
also provide information about language ancestry. Although we currently
lack rate estimates for structural data of the kind mentioned above,
some structural features are claimed to be highly stable (Nichols 1992)
and so may prove decisive in identifying long-range language
relationships. Indeed, some of the most promising recent research
testing deep ancestry hypotheses makes use of structural language
features. Dunn et al. (2005), for example, were able to use structural
data together with phylogenetic inference techniques from evolutionary
biology to identify historical signal in the Papuan languages likely to
date back over 10,000 years. More recently, Reesink, Singer and Dunn
(In press), have used structural data to classify the languages of the
ancient super-continent Sahul into recognized major groups, some of
which are likely to be just as old or perhaps much older. These
findings are among the first to demonstrate language relationships
beyond the traditionally held ~8ky limit. As in the case of the lexical
data, if a set of highly stable structural features can be identified,
it should be possible to push this time horizon back substantially
further.
From our origins in Africa, the story of human evolution is largely one
of cultural change. Language genealogies track cultures in a way that
genes cannot (Friedlaender et al. 2009) and so are crucial to our
understanding of human prehistory. The findings discussed here suggest
that we should in principle be able to trace language ancestry back
beyond the neolithic, perhaps even as far as our expansion from Africa.
Comparative analysis and hypothesis testing on a global scale will
require high-quality and easily accessible lexical and structural
language databases covering a large fraction of the world's languages.
Some important steps are now being taken in this direction (e.g., the
World Atlas of Language Stuctures (Haspelmath et al. 2005)) but more
work is needed along these lines if we are to fully capitalise on the
linguistic legacy of our cultural past.
References
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Menozzi, P. & Mountain, J. 1988 Reconstruction of human evolution:
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Dunn, M., Terrill, A., Reesink, G., Foley, R. A. & Levinson, S. C.
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language history. Science 309, 2072-2075.
Friedlaender, J., Hunley, K., Dunn, M., Terrill, A., Lindstrom, E.,
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Gray, R. D. 2005 Pushing the Time Barrier in the Quest for Language
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Reesink, G., Singer, R. & Dunn, M. In press Explaining the
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