Human pigmentation mega-study

A great new study on the genetics of human (including African) pigmentation. I would love to see a future study that would reconstruct what ancestral modern humans looked like pigmentation-wise, as this trait is tightly correlated with sun exposure (and thus latitude), and may thus pinpoint a narrow latitudinal zone where ancestral modern humans may have lived.

From a related story:

The most dramatic discovery concerned a gene known as MFSD12. Two mutations that decrease expression of this gene were found in high frequencies in people with the darkest skin. These variants arose about a half-million years ago, suggesting that human ancestors before that time may have had moderately dark skin, rather than the deep black hue created today by these mutations.

Science 12 Oct 2017: eaan8433 DOI: 10.1126/science.aan8433

Loci associated with skin pigmentation identified in African populations

Nicholas G. Crawford et al.

Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2 and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in southern Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of UV response genes under selection in Eurasians.

Link

Prehistoric farmers from northern Greece had lactose intolerance, brown eyes, dark skin

According to this:

Πολύ σημαντικό πρόσφατο εύρημα αποτελεί η ανάκτηση ολόκληρων γονιδιωμάτων από τρεις προϊστορικούς αγρότες, που έζησαν στη Βόρεια Ελλάδα 7.500 με 5.500 χρόνια πριν από σήμερα. Τα δεδομένα αυτά αναλύονται και αναμένεται να ρίξουν φως στις προγονικές σχέσεις των πρώτων Ευρωπαίων και να δώσουν πλήθος πληροφοριών, που συνδέονται με λειτουργικά και μορφολογικά χαρακτηριστικά. Ήδη, είναι γνωστό, ότι κάποιοι νεολιθικοί πρόγονοί μας δε μπορούσαν να πέψουν το γάλα, ήταν δηλαδή δυσανεκτικοί στη λακτόζη και είχαν καστανά μάτια και σκουρόχρωμη επιδερμίδα.

Related video:

Into, out of, and across the Eurasian steppe

A new paper in Nature adds to the earlier study in the same journal by presenting data from 101 ancient Eurasians. The year is not yet halfway over, but it seems that the ancient DNA field is moving towards a new norm of studying dozens of individuals at a time and comprehensively tackling the "big problems" that have vexed archaeologists, linguists, and historians for decades if not centuries.

The first conclusion of the new study is the detection of the migration from the steppe to Europe that was the title piece of the earlier study. The authors do not present quantitative estimates of the amount of demographic replacement effected by the Yamnaya-to-Corded Ware migration, so it will be interesting to see if there are any minor significant differences in these. But, the two papers have different Yamnaya and Corded Ware samples, and yet arrive at qualitatively similar conclusions, so at least this part of the story should be considered firmly "settled".

The second conclusion is the migration from the European steppe to the Afanasievo culture of the Altai. This has been long-hypothesized based on the physical type of the Afanasievo people and their possession of a similar pastoralist/wheeled vehicle toolkit that would have allowed them to cover the huge difference between Europe and the Altai. This confirms movement #2 of the Anthony/Ringe model, although I doubt that this migration had anything to do with Tocharians as detailed below. But, it did happen.

The third conclusion is that the later steppe cultures of the Sintashta and Andronovo (putative Indo-Iranians according to some), were not a continuation of the Yamnaya-Afanasievo people, but had extra Neolithic farmer ancestry. So, it seems that Neolithic farmers entered the steppe, and the development of steppe cultures did not happen in isolation. Whether this involved migration of Corded Ware people (as the authors prefer), who were already a mixture of Yamnaya and Neolithic farmers, or some other mixture of Neolithic farmers with steppe populations (e.g., Tripolye plus Yamnaya) remains to be seen.

The fourth conclusion of the paper is that these steppe cultures were also later replaced by people of at least partial East Asian or "Native American"-like ancestry.  So, it seems that movements into the steppe happened both on the western end (as the incursion of Neolithic farmer ancestry into the Sintashta proves), but also on the eastern end, with the Europeoid populations of western origin receiving admixture from the eastern periphery of the Eurasian steppe.

As for the Yamnaya, the authors do not find a very strong signal of admixture (as did the earlier study), which they attribute quite plausibly to the lack of eastern hunter-gatherers in their dataset. On the other hand, they claim that the "Caucasus" genetic component in the steppe populations was of steppe ancestry rather than Near Eastern/Caucasian origin as was claimed in the earlier paper. This is based on the statistic D(Yoruba, Armenia BA; Yamnaya, Corded Ware) that is not significantly different from zero. However, Corded Ware is a mixture of Yamnaya and European Neolithic, so the sign of this statistic is determined by the sign of the statistic D(Yoruba, Armenia BA; Yamnaya, European Neolithic). If Yamnaya was simply a steppe population, descendants of local people without ancestry from the Middle East/Caucasus, then this statistic would be positive because of the shared Middle Eastern ancestry of Armenia BA and European Neolithic. Whereas, if Yamnaya is a mixture of a steppe population and a Middle Eastern/Caucasian one, then the statistic would be positive/negative for the respective parts, which would be consistent with an average not different from zero. I am sure that when the new data is re-analyzed together with the eastern hunter-gatherers it will be clear that the Yamnaya are not a pure steppe population.

Nonetheless, I am quite glad to read a sentence such as this:

Populations in northern and central Europe were composed of a mixture of the earlier hunter-gatherer and Neolithic farmer10 groups, but received ‘Caucasian’ genetic input at the onset of the Bronze Age (Fig. 2).

It seems that my prediction the the West_Asian component would appear in post-5ka Europeans and was related to Indo-Europeans has been adequately confirmed by the last two papers.

Speaking of the Caucasus/Middle East, it seems clear as a first approximation that the Bronze Age Armenians are quite similar to modern Armenians. Whether the genetic continuity of Armenians extends beyond the Bronze Age, or Armenians were formed by mixture in the Bronze Age remains to be seen. The question of Armenian linguistic origins is of course separate as it is commonly understood that the Armenian language is unrelated to Anatolian languages and may have arrived in Armenia from the Balkans at around the Bronze Age-Iron Age transition.

The authors also study some phenotypic traits such as lactase peristence (Yamnaya had some, but overall prevalence was much lower than modern Europeans, hence lots of selection to the present), and skin eye pigmentation. Like Wilde et al., and Mathieson et al., the steppe populations seem to have had brown eyes. Given that so did Neolithic Europeans, and (presumably) ancient Middle Easterners/Caucasians, I think it's a good bet that Proto-Indo-Europeans (whatever solution to the PIE urheimat one accepts) were a brown-eyed people, or in the very least far from the blue-eyed "Aryans" of racial mythology. Even the Bronze Age and Iron Age Asians seem to have been a predominantly brown-eyed people, although the derived HERC2 allele seems to be at a higher frequency in them than in the steppe Europeans.

The story of the Y-chromosomes seems very interesting, although these are not resolved to fine detail. The most interesting aspect of this part of the work is the appearance of haplogroup J in Iron Age samples from Russia, Armenia, and the Altai. This may tie in to the question of the Tocharian origins, which I have claimed were associated with R1b, rather than R1a (as the Indo-Iranians were). The modern Uygurs (who are partially of Tocharian origin) have both J2 and R1b, so were the recipients of West Eurasian elements other than the R1a that so seem to have dominated the eastern steppe, including the Afanasievo. I continue to think there's no evidence that the Afanasievo is Proto-Tocharian, as it's in the wrong place and 3,000 years before the attestation of Tocharian. 

Overall this is an amazing study which adds a lot to what we know about Bronze Age Eurasia. Hopefully there is more to come in the second half of 2015, but for the time being there is plenty to chew on.

Nature 522, 167–172 (11 June 2015) doi:10.1038/nature14507

Population genomics of Bronze Age Eurasia

Morten E. Allentoft, Martin Sikora, Karl-Göran Sjögren, Simon Rasmussen, Morten Rasmussen, Jesper Stenderup, Peter B. Damgaard, Hannes Schroeder, Torbjörn Ahlström, Lasse Vinner, Anna-Sapfo Malaspinas, Ashot Margaryan, Tom Higham, David Chivall, Niels Lynnerup, Lise Harvig, Justyna Baron, Philippe Della Casa, Paweł Dąbrowski, Paul R. Duffy, Alexander V. Ebel, Andrey Epimakhov, Karin Frei, Mirosław Furmanek, Tomasz Gralak, Andrey Gromov, Stanisław Gronkiewicz, Gisela Grupe, Tamás Hajdu, Radosław Jarysz, Valeri Khartanovich, Alexandr Khokhlov, Viktória Kiss, Jan Kolář, Aivar Kriiska, Irena Lasak, Cristina Longhi, George McGlynn, Algimantas Merkevicius, Inga Merkyte, Mait Metspalu, Ruzan Mkrtchyan, Vyacheslav Moiseyev, László Paja, György Pálfi, Dalia Pokutta, Łukasz Pospieszny, T. Douglas Price, Lehti Saag, Mikhail Sablin, Natalia Shishlina, Václav Smrčka, Vasilii I. Soenov, Vajk Szeverényi, Gusztáv Tóth, Synaru V. Trifanova, Liivi Varul, Magdolna Vicze, Levon Yepiskoposyan, Vladislav Zhitenev, Ludovic Orlando, Thomas Sicheritz-Pontén, Søren Brunak, Rasmus Nielsen, Kristian Kristiansen & Eske Willerslev

The Bronze Age of Eurasia (around 3000–1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.

Link

101 ancient genomes from Bronze Age Eurasia

New data has been posted online. This seems related to this earlier post. Hopefully the study linked to this data will appear soon, but genome bloggers can get to it thanks to the early data release.

Investigation of Bronze Age in Eurasia by sequencing from 101 ancient human remains. 

The Bronze Age (BA) of Eurasia (c. 3,000-1,000 years BC, 3-1 ka BC) was a period of major cultural changes. Earlier hunter-gathering and farming cultures in Europe and Asia were replaced by cultures associated with completely new perceptions and technologies inspired by early urban civilization. It remains debated if these cultural shifts simply represented the circulation of ideas or resulted from large-scale human migrations, potentially also facilitating the spread of Indo-European languages and certain phenotypic traits. To investigate this and the role of BA in the formation of Eurasian genetic structure, we used new methodological improvements to sequence low coverage genomes from 101 ancient humans (19 > 1X average depth) covering 3 ka BC to 600 AD from across Eurasia. We show that around 3 ka BC, Central and Northern Europe and Central Asia receive genetic input through people related to the Yamnaya Culture from the Pontic-Caspian Steppe, resulting in the formation of the Corded Ware Culture in Europe and the Afanasievo Culture in Central Asia. A thousand years later, genetic input from North-Central Europe into Central Asia gives rise to the Sintashta and Andronovo Cultures. During the late BA and Iron Age, the European-derived populations in Asia are gradually replaced by multi-ethnic cultures, of which some relate to contemporary Asian groups, while others share recent ancestry with Native Americans. Our findings are consistent with the hypothesised spread of Indo-European languages during early BA and reveal that major parts of the demographic structure of present-day Eurasian populations were shaped during this period. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency during the BA, contrary to lactose tolerance, indicating a more recent onset of positive selection in the latter than previously believed.

Link

Bronze Age warrior from Poland

Google translation of original article:

Skull warrior was in such good condition that the museum was tempted by an experiment - a reconstruction of his face. Tasks undertaken by the research team of Dr. Dorothy Lorkiewicz-Muszyńska of the Department of Forensic Medicine, University of Medical Sciences. Every day with their ability to use the police, for example, when you need to identify a murder victim. The first step was to make a 3D scan of the skull.

- At the base using a special computer program was applied to the muscle tissue - explains the director Bartecki. - Method shows more than 90 percent. compliance with the real appearance of a man - says.

Proved invaluable assistance skeleton results Rogalin. Also genetic. Thanks to them, we know that the warrior had a dark complexion, dark hair and eyes.

This combination of traits is rather uncommon in modern Poles. It seems that eastern Europeans looked quite different four thousand years ago than they do today.

Dark pigmentation of Eneolithic and Bronze Age kurgan groups from eastern Europe

This is a very exciting new study that seems to parallel some results from early west Europeans. The authors invoke selection as a possible cause for the massive change in frequency between the Bronze Age and present-day Ukrainians.

An invocation of selection as an explanation requires evidence population continuity, otherwise changes in allele frequency may involve migration of a new frequency-differentiated new population; for example, the massive change in pigmentation in North America over the last 500 years is not due to selection but to migration of Europeans. The authors cannot reject population continuity on the basis of mtDNA haplogroup frequencies, although autosomal data may be more informative for that purpose.

In any case, the fact that the limited sample from western Europe and the much more extensive sample from eastern Europe both show a darker pigmentation than modern Europeans does suggest that interesting changes happened in Europe over the last few thousand years and samples from more recent time periods may better determine the pace of this change.

From the paper:

In sum, a combination of selective pressures associated with living in northern latitudes, the adoption of an agriculturalist diet, and assortative mating may sufficiently explain the observed change from a darker phenotype during the Eneolithic/Early Bronze age to a generally lighter one in modern Eastern Europeans, although other selective factors cannot be discounted. The selection coefficients inferred directly from serially sampled data at these pigmentation loci range from 2 to 10% and are among the strongest signals of recent selection in humans.

UPDATE: 

The classical Greeks did of course notice that the inhabitants of the north Pontic hinterland, collectively known as Scythians, were extraordinarily light-pigmented. This would imply that major pigmentation change occurred in the steppe over a time span of Bronze Age-Classical Antiquity rather than Bronze Age-present; this would imply even higher selection coefficients (if selection over a population exhibiting continuity is at play).

The Scythians were also thought to be recent arrivals from the east so it is not clear if they were descended from the Bronze Age population of eastern Europe; the crazy selection coefficients that would need to be assumed if there was indeed population continuity might imply that Herodotus got it right again, and the Scythians did in fact arrive from elsewhere. That would of course also imply that people from Central Asia and Siberia (where the Scythians may have come from) were originally lighter than Europeans which does find support from an older study on southern Siberian remains. Ironically, if that is the case, it would mean that the famous light-pigmented mummies of different parts of Inner Asia may not be long-lost European descendants -- as it has sometimes been presumed on the basis of modern-day clines of pigmentation. As usual, ancient DNA continues to surprise.

PNAS doi: 10.1073/pnas.1316513111

Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

Sandra Wilde et al.

Eye, hair, and skin pigmentation are highly variable in humans, particularly in western Eurasian populations. This diversity may be explained by population history, the relaxation of selection pressures, or positive selection. To investigate whether positive natural selection is responsible for depigmentation within Europe, we estimated the strength of selection acting on three genes known to have significant effects on human pigmentation. In a direct approach, these estimates were made using ancient DNA from prehistoric Europeans and computer simulations. This allowed us to determine selection coefficients for a precisely bounded period in the deep past. Our results indicate that strong selection has been operating on pigmentation-related genes within western Eurasia for the past 5,000 y.

Link

SLC24A5 light skin pigmentation allele origin

From the paper:

Adjustment for undercounting is substantial, increasing the estimated age for the combined samples to 12.4 (95% confidence interval 7.6−19.2) kya. If mutation rates in recent humans are lower than predicted from the human-chimpanzee divergence (Scally and Durbin 2012), true ages will be even older. Our adjusted dates overlap those previously reported (Beleza et al. 2012) and are also consistent with the lower limit for the origin of A111T set by the finding that the Alpine “iceman” dated to 5.3 kya was homozygous for this variant (Keller et al. 2012).

Related:

• Europeans and South Asians share by descent SLC24A5 light skin allele
• When Eurasians got lighter skin

Taking the 12.4ky estimate and multiplying by two (for the slower autosomal mutation rate) yields an estimate of 25ky, so it seems that this allele did not accompany the earliest modern human colonists of West Eurasia but emerged in some region and spread from there. It will be interesting to see (through ancient DNA) by what processes of migration, admixture, and selection this transpired.

G3 doi: 10.1534/g3.113.007484

Molecular Phylogeography of a Human Autosomal Skin Color Locus Under Natural Selection

Victor A. Canfield et al.

Divergent natural selection caused by differences in solar exposure has resulted in distinctive variations in skin color between human populations. The derived light skin color allele of the SLC24A5 gene, A111T, predominates in populations of Western Eurasian ancestry. To gain insight into when and where this mutation arose, we defined common haplotypes in the genomic region around SLC24A5 across diverse human populations and deduced phylogenetic relationships between them. Virtually all chromosomes carrying the A111T allele share a single 78-kb haplotype that we call C11, indicating that all instances of this mutation in human populations share a common origin. The C11 haplotype was most likely created by a crossover between two haplotypes, followed by the A111T mutation. The two parental precursor haplotypes are found from East Asia to the Americas but are nearly absent in Africa. The distributions of C11 and its parental haplotypes make it most likely that these two last steps occurred between the Middle East and the Indian subcontinent, with the A111T mutation occurring after the split between the ancestors of Europeans and East Asians.

Link

Europeans and South Asians share by descent SLC24A5 light skin allele

The age estimate for this allele is quite old but with a huge 95% confidence interval. Hopefully ancient DNA can illuminate the trajectory of the allele's frequency through time and space.

Razib has more.

PLoS Genet 9(11): e1003912. doi:10.1371/journal.pgen.1003912

The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent

Chandana Basu Mallick et al.

Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.

Link

Admixture and pigmentation in Cape Verde

The interesting thing about this paper is that it shows that one can explain skin color in people from Cape Verde better if one uses their proportion of African/European admixture, rather than by looking at individuals' genotypes at loci associated with the trait. This probably means that many loci of minor effect on the trait differentiate Europeans from Africans.

Prediction of skin color based on ancestry is much better than prediction of eye color from the same, which is not surprising since skin color is a highly polygenic trait.

PLoS Genet 9(3): e1003372. doi:10.1371/journal.pgen.1003372

Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

Sandra Beleza et al.

Abstract

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10−62, SLC24A5 P = 9.6×10−9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10−27, TYR P = 1.1×10−9, APBA2[OCA2] P = 1.5×10−8, SLC45A2 P = 6×10−9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

Link

GWAS study of pigmentation in four European countries

From the paper:

Males (M) have consistently lighter pigmentation (lower scored) than females (F) in all four countries. Among countries, the largest pigmentation difference is with Ireland, where, in our sample, individuals have lighter pigmentation or lower M index on average than in Poland, Italy, or Portugal. Hair pigmentation histogram (C) and boxplot by country (D) in 341 individuals showing the distribution of hair pigmentation and the differences among countries. In our sample, individuals from Northern European countries (Ireland, Poland) have on average lighter hair pigmentation than individuals from Southern European countries (Italy, Portugal). The distributions in males are similar to those in females in all countries except Ireland, where, in our sample, males have darker hair color than females (not shown). Eye pigmentation histogram (E) and boxplot by country (F) in 468 individuals showing the bimodal distribution of eye pigmentation and the differences among countries. Comparison with self-reported phenotypes shows that the two modes of the distribution correspond to blue and brown eye color, while individuals reporting green and hazel eye color have intermediate C’ values. As with hair pigmentation, in our sample, individuals from Northern European countries have on average lighter eye pigmentation than individuals from Southern European countries. 

...   

Interestingly, our analysis of variation in skin color in Europe demonstrates a consistent difference in skin color between the sexes. By the DermaSpectrometer M index measure, males are more lightly pigmented than females in each of the four European countries we studied. The same trend in M index was reported previously in a sample of European Americans [38]. Our results in populations of European ancestry contradict earlier anthropological studies that have concluded females are more lightly pigmented than males in most populations (reviewed in [2]). One potential reason for the conflicting results is the different instruments used. In early studies, which used the Evans Electric Limited (EEL) and Photovolt broad-spectrum spectrophotometers, skin pigmentation estimates may be confounded by the hemoglobin level to a greater extent than for the DermaSpectrometer used in the present study [46].

Some data (lower = lighter):

One thing of interest is that while Irish males/females are both lighter-eyed than other Europeans, including Poles from northern Europe, Irish females appear to be lighter-haired than Irish males (96.3 vs. 106.7), but no such substantial sex difference exists in the Poles in this trait (107.5 vs. 109.5). Sexual dimorphism seems to lean in the direction of lighter male skins and lighter female hair across the four countries.

Peter Frost has offered the theory that "gentlemen prefer blondes" because during the Ice Age boreal hunters lived a harsh lifestyle that killed many of them, but the remainder could not adopt a polygynous lifestyle, because provisioning for a wife was expensive. As a result, women had to compete for the remaining men, and men could be picky, preferring those with a "rare color advantage." It is not immediately clear to me how this might explain the Ireland vs. Poland differentiation, assuming it reflects a broader NW/NE trend, since NE Europeans are more likely to be descended from hunter-gatherers of the tundra-steppe.

PLoS ONE 7(10): e48294. doi:10.1371/journal.pone.0048294

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

Sophie I. Candille et al.

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.

Link

When Eurasians got lighter skin

My default position is to doubt all molecular dates until I understand how they were derived. Nonetheless, these results seem broadly consistent with the idea that Eurasian modern humans got lighter as their ancestors moved into more northern latitudes of the Old World and replaced Neandertals and others earlier Eurasian occupants, and then they got really lighter post-LGM, and then some got really really lighter with mutations in genes such as SLC24A4 (not studied here).

I suppose we will really find out who got what mutation when only through ancient DNA.

Mol Biol Evol (2012) doi: 10.1093/molbev/mss207

The timing of pigmentation lightening in Europeans

Sandra Belezal et al.

The inverse correlation between skin pigmentation and latitude observed in human populations is thought to have been shaped by selective pressures favoring lighter skin in order to facilitate vitamin D synthesis in regions far from the equator. Several candidate genes for skin pigmentation have been shown to exhibit patterns of polymorphism that overlap the geospatial variation in skin color. However, little work has focused on estimating the timeframe over which skin pigmentation has changed and on the intensity of selection acting on different pigmentation genes. To provide a temporal framework for the evolution of lighter pigmentation, we used forward Monte Carlo simulations coupled with a rejection sampling algorithm to estimate the time of onset of selective sweeps and selection coefficients at four genes associated with this trait in Europeans: KITLG, TYRP1, SLC24A5, and SLC45A2. Using compound haplotype systems consisting of rapidly evolving microsatellites linked to one SNP in each gene, we estimate that the onset of the sweep shared by Europeans and East Asians at KITLG occurred about 30,000 years ago, after the out-of-Africa migration, while the selective sweeps for the European-specific alleles at TYRP1, SLC24A5, and SLC45A2 started much later, within the last 11,000-19,000 years, well after the first migrations of modern humans into Europe. We suggest that these patterns were influenced by recent increases in size of human populations, which favored the accumulation of advantageous variants at different loci.

Link

SMBE 2012 abstracts (Part II)

Some more abstracts from SMBE 2012.

The Neolithic trace in mitochondrial haplogroup U8 

Joana Barbosa Pereira 1,2 , Marta Daniela Costa 1,2 , Pedro Soares 2 , Luísa Pereira 2,3 , Martin Brian Richards 1,4 1 Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, 2 Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal,  3 Faculdade de Medicina da  Universidade do Porto, Porto, Portugal,  4 School of Applied Sciences, University of Huddersfield, Huddersfield, UK  

The mitochondrial DNA (mtDNA) still remains an important marker in the study of human history, especially if  considering the increasing amount of data available. Among the several questions regarding human history that are  under debate, the model of expansion of agriculture into Europe from its source in the Near East is still unclear. Recent  studies have indicated that clusters belonging to haplogroup K, a major clade from U8, might be related with the  Neolithic expansions. Therefore, it is crucial to identify the founder lineages of the Neolithic in Europe so that we may  understand the real genetic input of the first Near Eastern farmers in the current European population and comprehend  how agriculture spread so quickly throughout all Europe.  In order to achieve this goal, a total of 55 U8 samples from the Near East, Europe and North Africa were selected for  complete characterisation of mtDNA. A maximum-parsimonious phylogenetic tree was constructed using all published  sequences available so far. Coalescence ages of specific clades were estimated using ρ statistic, maximum likelihood  and Bayesian methods considering a mutation rate for the complete molecule corrected for purifying selection.   Our results show that U8 dates to ~37-54 thousand years ago (ka) suggesting that this haplogroup might have been  carried by the first modern humans to arrive in Europe, ~50 ka. Haplogroup K most likely originated in the Near East  ~23-32 ka where it might have remained during the Last Glacial Maximum, between 26-19 years ago. The majority of K  subclades date to the Late Glacial and are related with the repopulation of Europe from the southern refugia areas. Only  a few lineages appear to reflect post glacial, Neolithic or post-Neolithic expansions, mostly occurring within Europe. The  major part of the lineages dating to the Neolithic period seems to have an European origin with exception of haplogroup  K1a4 and K1a3. Clade K1a4 appears to be originated from the Near East where it also reaches its highest peak of  diversity. Despite the main clades of K1a4 arose in the Near East during the Late Glacial, its subclade K1a4a1 dates to  ~9-11 ka and is most likely related with the Neolithic dispersal to Europe. Similarly, K1a3 probably originated in the Near  East during the Late Glacial and its subclade K1a1a dispersed into Europe ~11-13 ka alongside with the expansion of  agriculture. 

Late Glacial Expansions in Europe revealed through the fine-resolution characterisation of mtDNA haplogroup  U8 

Marta Daniela Costa 1,2 , Joana Barbosa Pereira 1,2 , Pedro Soares 2 , Luisa Pereira 2,3 , Martin Brian Richards 1,4 1 Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, 2 IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal,  3 Faculdade de  Medicina, Universidade do Porto, Porto, Portugal,  4 School of Applied Sciences, University of Huddersfield, Huddersfield,  UK  

The maternally inherited and fast evolving mitochondrial DNA (mtDNA) molecule is a highly informative tool with which  to reconstruct human prehistory. This has become even more true in recent years, as mtDNA based studies are  becoming more robust and powerful due to the availability of complete mtDNA genomes. These allow better mutation  rate estimates and fine-resolution characterisation of the phylogeography of mtDNA haplogroups, or named  clades.  MtDNA haplogroup K, the major subclade of U8, occurs at low frequencies through West Eurasian populations,  and is much more common in Ashkenazi Jews. However, the lack of variation on the first hypervariable segment (HVSI) has precluded any meaningful phylogeographic analysis to date. We therefore completely sequenced 50 haplogroup  K and 5 non-K U8 mtDNA samples from across Europe and the Near East, and combined them with 343 genomes  previously deposited in GenBank, in order to reconstruct a detailed phylogenetic tree. By combining several inference  methods, including maximum parsimony, maximum likelihood and Bayesian inference it was possible to trace the  timescale and geography of the main expansions and dispersals associated with this lineage. We confirmed that  haplogroup K, dating to ~32 thousand years (ka) ago, descended from the U8 clade, which coalesces ~48 ka ago. The  latter is close to the timing of the first arrival of modern humans in Europe and U8 could be one of the few surviving  mtDNA lineages brought by the first settlers from the Near East. U8 split into the widespread U8b, at ~43 ka, and U8a,  which seems to have expanded only in Europe ~24 ka ago. Considering the pattern of diversity and the geographic  distribution, haplogroup K is most likely to have arisen in the Near East, ~32 ka ago. However, some subclades were  evidently carried to Europe during the Last Glacial Maximum (LGM). We observed significant expansions of haplogroup  K lineages in the Late Glacial period (14-19 ka), reflecting expansions out of refuge areas in southwest and possibly  also southeast Europe. 

Reticulated origin of domesticated tetraploid wheat 

Peter Civan Centro de Ciencias do Mar, Universidade do Algarve, Faro, Portugal  

The past 15 years have witnessed a notable scientific interest in the topic of crop domestication and the emergence of  agriculture in the Near East. Multi-disciplinary approaches brought a significant amount of new data and a multitude of  hypotheses and interpretations. However, some seemingly conflicting evidence, especially in the case of emmer wheat,  caused certain controversy and a broad scientific consensus on the circumstances of the wheat domestication has not  been reached, yet.  The past phylogenetic research has translated the issue of wheat domestication into somewhat simplistic mono- /polyphyletic dilemma, where the monophyletic origin of a crop signalizes rapid and geographically localized  domestication, while the polyphyletic evidence suggests independent, geographically separated domestication events.  Interestingly, the genome-wide and haplotypic data analyzed in several studies did not yield consistent results and the  proposed scenarios are usually in conflict with the archaeological evidence of lengthy domestication.  Here I suggest that the main cause of the above mentioned inconsistencies might lie in the inadequacy of the divergent,  tree-like evolutional model. The inconsistent phylogenetic results and implicit archaeological evidence indicate a  reticulate (rather than divergent) origin of domesticated emmer. Reticulated genealogy cannot be properly represented  on a phylogenetic tree; hence different sets of samples and genetic loci are prone to conclude different domestication  scenarios. On a genome-wide super-tree, the conflicting phylogenetic signals are suppressed and the origin of  domesticated crop may appear monophyletic, leading to misinterpretations of the circumstances of the Neolithic  transition.  The network analysis of multi-locus sequence data available for tetraploid wheat clearly supports the reticulated origin of  domesticated emmer and durum wheat. The concept of reticulated genealogy of domesticated wheat sheds new light  onto the emergence of Near-Eastern agriculture and is in agreement with current archaeological evidence of protracted  and dispersed emmer domestication.

High-coverage population genomics of diverse African hunter-gatherers 

Joseph Lachance 1 , Benjamin Vernot 2 , Clara Elbers 1 , Bart Ferwerda 1 , Alain Froment 3 , Jean-Marie Bodo 4 , Godfrey  Lema 5 , Thomas Nyambo 5 , Timothy Rebbeck 1 , Kun Zhang 6 , Joshua Akey 2 , Sarah Tishkoff 1 1 University of Pennsylvania, Philadelphia, PA, USA,  2 University of Washington, Seattle, WA, USA,  3 IRD-MNHN, Musee  de l'Homme, Paris, France,  4 Ministere de la Recherche Scientifique et de l’Innovation, Yaounde, Cameroon,  5 Muhimbili  University College of Health Sciences, Dar es Salaam, Tanzania,  6 University of California at San Diego, San Diego, CA,  USA     

In addition to their distinctive subsistence patterns, African hunter-gatherers belong to some of the most genetically  diverse populations on Earth.  To infer demographic history and detect signatures of natural selection, we sequenced  the whole genomes of five individuals in each of three geographically and linguistically diverse African hunter-gatherer  populations at >60x coverage.  In these 15 genomes we identify 13.4 million variants, many of which are novel,  substantially increasing the set of known human variation.  These variants result in allele frequency distributions that are  free of SNP ascertainment bias.  This genetic data is used to infer population divergence times and demographic history  (including population bottlenecks and inbreeding).  We find that natural selection continues to shape the genomes of  hunter-gatherers, and that deleterious genetic variation is found at similar levels for hunter-gatherers and African  populations with agricultural or pastoral subsistence patterns.  In addition, the genomes of each hunter-gatherer  population contain unique signatures of local adaptation.  These highly-divergent genomic regions include genes  involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing.

Reconstructing past Native American genetic diversity in Puerto Rico from contemporary populations Marina Muzzio 1,2 , Fouad Zakharia 1 , Karla Sandoval 1 , Jake K. Byrnes 3 , Andres Moreno-Estrada 1 , Simon Gravel 1 , Eimear  Kenny 1 , Juan L. Rodriguez-Flores 5 , Chris R. Gignoux 6 , Wilfried Guiblet 4 , Julie Dutil 7 , The 1000 Genomes Consortium 0 ,  Andres Ruiz-Linares 8 , David Reich 9,10 , Taras K. Oleksyk 4 , Juan Carlos Martinez-Cruzado 4 , Esteban Gonzalez  Burchard 6 , Carlos D. Bustamante 1 1 Department of Genetics, Stanford University School of Medicine, Stanford, California, USA,  2 Facultad de Ciencias  Naturales, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina,  3 Ancestry. com®, San Francisco,  California, USA,  4 Department of Biology, University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico,  5 Department  of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA,  6 Institute for Human Genetics,  University of California San Francisco, San Francisco, California, USA,  7 Ponce School of Medicine, Ponce, Puerto Rico, 8 Department of Genetics, Evolution and Environment. University College London, London, UK,  9 Department of  Genetics, Harvard Medical School, Boston, Massachusetts, USA,  10 Broad Institute of MIT and Harvard, Cambridge,  Massachusetts, USA  

The Caribbean region has a rich cultural and biological diversity, including several countries with different languages,  and important historical events like the arrival of the Europeans in the late fifteenth century affected it deeply. Although it  has been said that two main Native American groups peopled the Caribbean at the time of Columbus’s voyages—the  Arawakan-speaking Tainos and the Caribs—this model has been questioned because it comes from the descriptions  written by the conquerors. The archaeological record shows a richer picture of trade among the islands, cultural change  and diversity than what colonial documents depict, from the early settlements around 8000 B.P. to the chiefdoms and  towns at the time of contact. How this area was peopled and how its inhabitants interacted with the surrounding  continent are questions that remain to be answered due to the fragmentary nature of the historical and archaeological  records.   
We aim to reconstruct the Native American genetic diversity from the time of the Spanish arrival at the island of Puerto  Rico from its contemporary population. We seek to find out how the original peopling of Puerto Rico occurred, along  with which contemporary Native American populations are the most closely related to the Native tracks found. We used  PCAdmix to trace Native American segments in admixed individuals, thus enabling us to reconstruct the original native  lineages previous to the European and African contact.   

Specifically, we generated local ancestry calls for the 70 parents of the 35 complete Puerto Rican trios from the wholegenome and Illumina Omni 2.5M chip Genotype data of the 1000 Genomes Project, both to examine genome-wide  admixture patterns and to infer demographic historical events from ancestry tract length distributions and an ancestryspecific PCA approach, adding 55 Native American groups as potential source populations (N=475 genotyped through  Illumina’s 650K array) and 15 selected Mexican trios (genotyped on Affymetrix’s 6.0 array, including about 906,000  SNPs) to provide population context. ADMIXTURE analysis has shown that in Puerto Rico there is no single source of  contribution for the Native component. Rather, this component seems to include a mixture of major Mexican and  Andean components with little contributions from the Amazonian isolates. On the other hand, the ancestry-specific PCA  plotted the Puerto Rican Native segments tightly clustered with the Native segments of groups from the same language  family as the Tainos (Equatorial-Tucanoan), showing a clear association between linguistics and genetics instead of a  geographical one.

 Inference of demographic history and natural selection in African Pygmy populations from whole-genome  sequencing data

 Martin Sikora 1 , Etienne Patin 2 , Helio Costa 1 , Katherine Siddle 2 , Brenna M Henn 1 , Jeffrey M Kidd 1,3 , Ryosuke Kita 1 ,  Carlos D Bustamante 1 , Lluis Quintana-Murci 2 1 Department of Genetics, School of Medicine, Stanford Uni, Stanford, CA, USA,  2 Unit of Human Evolutionary Genetics,  Institut Pasteur, CNRS URA3012, Paris, France,  3 Departments of Human Genetics and Computational Medicine and  Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA     

The Pygmy populations of Central Africa are some of the last remaining hunter-gatherers among present-day human  populations, and can be broadly classified into two geographically separated groups, the Western and Eastern Pygmies.  Compared to their neighboring populations of predominantly Bantu origin, Pygmy populations show distinct cultural and  physical characteristics, most notably short stature, often referred to as the “Pygmy phenotype”. Given their distinct  physical characteristics, the questions of the demographic history and origin of the Pygmy phenotype have attracted  much attention. Previous studies have shown an ancient divergence (~60,000 years ago) of the ancestors of modernday Pygmies from non-Pygmies, and a more recent split of the Eastern and Western Pygmy groups. However, these  studies were generally based on a relatively small set of markers, precluding accurate estimations of demographic  parameters. Furthermore, despite the considerable interest, to date there is still little known about the genetic basis of  the small stature phenotype of Pygmy populations.   

In order to address these questions, we sequenced the genomes of 47 individuals from three populations: 20 Baka, a  Pygmy hunter-gatherer population from the Western subgroup of the African Pygmies; 20 Nzebi, a neighboring nonPygmy agriculturist population from the Bantu ethnolinguistic group; as well as 7 Mbuti, Eastern Pygmy population, from  the Human Genome Diversity Project (HGDP). We performed whole-genome sequencing using Illumina Hi-Seq 2000 to  a median sequencing depth of 5.5x per individual. After stringent quality control filters, we call over 17 Million SNPs  across the three populations, 32% of them novel (relative to dbSNP 132). Genotype accuracy after imputation was  assessed using genotype data from the Illumina OMNI1 SNP array, and error rates were found to be comparable to  other low-coverage studies (< 3% for most individuals). Preliminary results show relatively low genetic differentiation  between the Baka and the Nzebi (mean FST = 0.026), whereas the Mbuti show higher differentiation to both Baka and  Nzebi (mean FST = 0.060 and 0.070, respectively). Furthermore, we find that alleles previously found to be associated with height in other populations are not enriched for the “small” alleles in the Pygmy populations. We find a number of  highly differentiated genomic regions as candidate loci for height differentiation, which will be verified using simulations  under the best-fit demographic model, inferred from multi-dimensional allele frequency spectra using DaDi. Our dataset  will allow a detailed investigation of the demographic history and the genomics of adaptation in these populations.

Genetic structure in North African human populations and the gene flow to Southern Europe

Laura R Botigué 1 , Brenna M Henn 2 , Simon Gravel 2 , Jaume Bertranpetit 1 , Carlos D Bustamante 2 , David Comas 1 1 Institut de Biologia Evolutiva (IBE, CSIC-UPF), Barcelona, Spain,  2 Stanford University, Stanford CA, USA Despite being in the African continent and at the shores of the Mediterranean, North African populations might have  experienced a different population history compared to their neighbours. However, the extent of their genetic divergence  and gene flow from neighbouring populations is poorly understood. In order to establish the genetic structure of North  Africans and the gene flow with the Near East, Europe and sub-Saharan Africa, a genomewide SNP genotyping array  data (730,000 sites) from several North African and Spanish populations were analysed and compared to a set of  African, European and Middle Eastern samples. We identify a complex pattern of autochthonous, European, Near  Eastern, and sub-Saharan components in extant North African populations; where the autochthonous component  diverged from the European and Near Eastern component more than 12,000 years ago, pointing to a pre-Neolithic  ‘‘back-to-Africa’’ gene flow. To estimate the time of migration from sub-Saharan populations into North Africa, we  implement a maximum likelihood dating method based on the frequency and length distribution of migrant tracts, which  has suggested a migration of western African origin into Morocco ~1,200 years ago and a migration of individuals with  Nilotic ancestry into Egypt ~ 750 years ago.  We characterize broad patterns of recent gene flow between Europe and Africa, with a gradient of recent African  ancestry that is highest in southwestern Europe and decreases in northern latitudes. The elevated shared African  ancestry in SW Europe (up to 20% of the individuals’ genomes) can be traced to populations in the North African  Maghreb. Our results, based on both allele-frequencies and shared haplotypes, demonstrate that recent migrations from  North Africa substantially contribute to the higher genetic diversity in southwestern Europe

Estimating a date of mixture of ancestral South Asian populations

Priya Moorjani 1,2 , Nick Patterson 2 , Periasamy Govindaraj 3 , Danish Saleheen 4 , John Danesh 4 , Lalji Singh* 3,5 ,  Kumarasamy Thangaraj* 3 , David Reich* 1,2 1 Harvard University, Boston, Massachusetts, USA,  2 Broad Institute, Cambridge, Massachusetts, USA,  3 Centre for  Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India,  4 Dept of Public Health and Care, University of  Cambridge, Cambridge, UK,  5 Genome Foundation, Hyderabad, Andhra Pradesh, India Linguistic and genetic studies have demonstrated that almost all groups in South Asia today descend from a mixture of  two highly divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners and  Europeans, and Ancestral South Indians (ASI) not related to any populations outside the Indian subcontinent. ANI and  ASI have been estimated to have diverged from a common ancestor as much as 60,000 years ago, but the date of the  ANI-ASI mixture is unknown. Here we analyze data from about 60 South Asian groups to estimate that major ANI-ASI  mixture occurred 1,200-4,000 years ago. Some mixture may also be older—beyond the time we can query using  admixture linkage disequilibrium—since it is universal throughout the subcontinent: present in every group speaking  Indo-European or Dravidian languages, in all caste levels, and in primitive tribes. After the ANI-ASI mixture that  occurred within the last four thousand years, a cultural shift led to widespread endogamy, decreasing the rate of  additional mixture.   

Long IBD in Europeans and recent population history 

Peter Ralph, Graham Coop  UC Davis, Davis, CA, USA  

Numbers of common ancestors shared at various points in time across populations  can tell us about recent demography, migration, and population movements.  These rates of shared ancestry over tens of generations can be inferred from  genomic data, thereby dramatically increasing our ability to infer population  history much more recent than was previously possible with population genetic  techniques.  We have analyzed patterns of IBD in a dataset of thousands of  Europeans from across the continent, which provide a window into recent  European geographic structure and migration.   

Gene flow between human populations during the exodus from Africa, and the timeline of recent human  evolution  

Aylwyn Scally, Richard Durbin  Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK 

We present a novel test for historical gene flow between populations using unphased genotypes in present-day  individuals, based on the sharing of derived alleles and making a minimal set of assumptions about their demographic  history. We apply this test to data for three human individuals of African, European and Asian ancestry. We find that the  joint distribution of European and Asian genotypes is compatible with these populations having separated cleanly at  some time in the past without subsequent genetic exchange. However the same is not true of the European-African and  Asian-African distributions, which instead suggest an extended period of continued exchange between African and nonAfrican populations after their initial separation. 

We discuss this in comparison with recent models and estimates of separation time between these populations. We  also consider the impact of recent direct experimental studies of the human mutation rate, which suggest rates of  around 0.5 × 10 -9  bp -1  y -1 , substantially lower than prior estimates of 1 × 10 -9  bp -1  y -1  obtained from calibration against  the primate fossil record. We show that in several places the lower rate, implying older dates, yields better agreement  between genetic and non-genetic (paleoanthropological and archaeological) evidence for events surrounding the  exodus of modern humans from Africa and their dispersion worldwide.

Long-term presence versus recent admixture: Bayesian and approximate-Bayesian analyses of genetic  diversity of human populations in Central Asia 

Friso Palstra, Evelyne Heyer, Frederic Austerlitz  Eco-anthropologie et Ethnobiologie UMR 7206 CNRS, Equipe Genetique des Populations Humaines, Museum National  d'Histoire Naturelle, Paris, France 

A long-standing goal in population genetics is to unravel the relative importance of evolutionary forces that shape  genetic diversity. Here we focus on human populations in Central Asia, a region that has long been known to contain  the highest genetic diversity on the Eurasian continent. However, whether this variation principally reflects long-term  presence, or rather the result of admixture associated with repeated migrations into this region in more recent historical  times, remains unclear. Here we investigate the underlying demographic history of Central Asian populations in explicit  relation to Western Europe, Eastern Asia and the Middle East. For this purpose we employ both full Bayesian and  approximate-Bayesian analyses of nuclear genetic diversity in 20 unlinked non-coding resequenced DNA regions,  known to be at least 200 kb apart from any known gene, mRNA or spliced EST (total length of 24 kb), and 22 unlinked  microsatellite loci.   

Using an approximate Bayesian framework, we find that present patterns of genetic diversity in Central Asia may be  best explained by a demographic history which combines long-term presence of some ethnic groups (Indo-Iranians)  with a more recent admixed origin of other groups (Turco-Mongols). Interestingly, the results also provide indications  that this region might have genetically influenced Western European populations, rather than vice versa. A further  evaluation in MCMC-based Bayesian analyses of isolation-with-migration models confirms the different times of  establishment of ethnic groups, and suggests gene flow into Central Asia from the east. The results from the  approximate Bayesian and full Bayesian analyses are thus largely congruent. In conclusion, these analyses illustrate  the power of Bayesian inference on genetic data and suggest that the high genetic diversity in Central Asia reflects both  long-term presence and admixture in more recent historical times. 

Population structure and evidence of selection in the Khoe-San and Coloured populations from southern Africa 

Carina Schlebusch 1 , Pontus Skoglund 1 , Per Sjödin 1 , Lucie Gattepaille 1 , Sen Li 1 , Flora Jay 2 , Dena Hernandez 3 , Andrew  Singleton 3 , Michael Blum 2 , Himla Soodyall 4,5 , Mattias Jakobsson 1 1 Uppsala University, Uppsala, Sweden,  2 Université Joseph Fourier, Grenoble, France,  3 National Institute on Aging (NIH),  Bethesda, USA,  4 University of the Witwatersrand, Johannesburg, South Africa,  5 National Health Laboratory Service,  Johannesburg, South Africa  

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of  hunter-gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking  groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Mitochondrial DNA, Y-chromosome  and autosomal studies conducted on a few San groups revealed that they harbour some of the most divergent lineages  found in living peoples throughout the world.   

We used autosomal data to characterize patterns of genetic variation among southern African individuals in order to  understand human evolutionary history, in particular the demographic history of Africa. To this end, we successfully  genotyped ~ 2.3 million genome wide SNP markers in 220 individuals, comprising seven Khoe-San, two Coloured and  two Bantu-speaking groups from southern Africa. After quality filtering, the data were combined with publicly available  SNP data from other African populations to investigate stratification and demography of African populations.  

We also  applied a newly developed method of estimating population topology and divergence times. Genotypes and inferred  haplotypes were used to assess genetic diversity, patterns of haplotype variation and linkage disequilibrium in different  populations.  We found that six of the seven Khoe-San populations form a common population lineage basal to all other modern  human populations. The studied Khoe-San populations are genetically distinct, with diverse histories of gene flow with  surrounding populations. A clear geographic structuring among Khoe-San groups was observed, the northern and  southern Khoe-San groups were most distinct from each other with the central Khoe-San group being intermediate. The  Khwe group contained variation that distinguished it from other Khoe-San groups. Population divergence within the  Khoe-San group is approximately 1/3 as ancient as the divergence of the Khoe-San as a whole to other human  populations (on the same order as the time of divergence between West Africans and Eurasians). Genetic diversity in  some, but not all, Khoe-San populations is among the highest worldwide, but it is influenced by recent admixture. We  furthermore find evidence of a Nilo-Saharan ancestral component in certain Khoe-San groups, possibly related to the  introduction of pastoralism to southern Africa.   

We searched for signatures of selection in the different population groups by scanning for differentiated genome-regions  between populations and scanning for extended runs of haplotype homozygosity within populations. By means of the  selection scans, we found evidence for diverse adaptations in groups with different demographic histories and modes of  subsistence. 

Impacts of life-style on human evolutionary history: A genome-wide comparison of herder and farmer  populations in Central Asia 

Michael C. Fontaine 1,2 , Laure Segurel 2,3 , Christine Lonjou 4 , Tatiana Hegay 5 , Almaz Aldashev 6 , Evelyne Heyer 2 , Frederic  Austerlitz 1,2 1 Ecology, Systematics & Evolution. UMR8079 Univ. Paris Sud - CNRS - AgroParisTech, Orsay, France,  2 EcoAnthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Univ Paris Diderot, Sorbonne Paris Cite, Paris, France, 3 Department of Human Genetics, University of Chicago, Chicago, USA,  4 C2BiG (Centre de  Bioinformatique/Biostatistique Genomique d’Ile de France), Plateforme Post-genomique P3S, Hopital Pitie Salpetriere,  Paris, France,  5 Uzbek Academy of Sciences, Institute of Immunology, Tashkent, Uzbekistan,  6 Institute of Molecular  Biology and Medicine, National Center of Cardiology and Internal Medicine, Bishkek,  

Kyrgyzstan Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of habitats and  dietary components. These aspects of human environments have changed dramatically during human evolution, giving  rise to new selective pressures. Here we focused on two populations in Central Asia with long-term contrasted lifestyles:  Kyrgyz’s that are traditionally nomadic herders, with a traditional diet based on meat and milk products, and Tajiks that  are traditionally agriculturalists, with a traditional diet based mostly on cereals. We genotyped 93 individuals for more  than 600,000 SNP markers (Human-660W-Quad-V1.0 from Illumina) spread across the genome. We first analysed the  population structure of these two populations in the world-wide context by combining our results with other available  genome-wide data. Principal component and Bayesian clustering analyses revealed that Tajiks and Kirgiz’s are both  admixed populations which differed however from each other with respect to their ancestry proportions: Tajiks display a  much larger proportion of common ancestry with European populations while Kirgiz’s share a larger common ancestry  with Asiatic populations. We then examined the region of the genome displaying unusual population differentiation  between these two populations to detect natural selection and checked whether they were specific to Central Asia or  not. We complemented these analyses with haplotype-based analyses of selection. 

Bayesian inference of the demographic history of Niger-Congo speaking populations 

Isabel Alves 1,2 , Lounès Chikhi 2,3 , Laurent Excoffier 1,4 1 CMPG, Institute of Ecology and Evolution, Berne, Switzerland,  2 Population and Conservation Genetics Group, Instituto  Gulbenkian de Ciência, Oeiras, Portugal,  3 CNRS, Université Paul Sabatier, ENFA, Toulouse, France,  4 Swiss Institute of  Bioinformatics, Lausanne, Switzerland  

The Niger-Congo phylum encompasses more than 1500 languages spread over sub-Saharan Africa. This current wide  range is mostly due to the spread of Bantu-speaking people across sub-equatorial regions in the last 4000-5000 years.  Although several genetic studies have focused on the evolutionary history of Bantu-speaking groups, much less effort  has been put into the relationship between Bantu and non-Bantu Niger-Congo groups. Additionally, archaeological and  linguistic evidence suggest that the spread of these populations occurred in distinct directions from the core region  located in what is now the border between Nigeria and Cameroon towards West and South Africa, respectively. We  have performed coalescent simulations within an approximate Bayesian computation (ABC) framework in order to  statistically evaluate the relative probability of alternative models of the spread of Niger-Congo speakers and to infer  demographic parameters underlying these important migration events. We have analysed 61 high-quality microsatellite  markers, genotyped in 130 individuals from three Bantu and three non Bantu-speaking populations, representing a  "Southern wave" or the Bantu expansion, and a "Western wave", respectively. Preliminary results suggest that models  inspired by a spatial spread of the populations are better supported than classical isolation with migration (IM) models.  We also find that Niger-Congo populations currently maintain high levels of gene flow with their neighbours, and that  they expanded from a single source between 200 and 600 generations, even though available genetic data do not  provide enough information to accurately infer these demographic parameters.

A genetic study of skin pigmentation variation in India  

Mircea Iliescu1 , Chandana Basu Mallick 2,3 , Niraj Rai 4 , Anshuman Mishra 4 , Gyaneshwer Chaubey 2 , Rakesh Tamang 4 ,  Märt Möls 3 , Rie Goto 1 , Georgi Hudjashov 2,3 , Srilakshmi Raj 1 , Ramasamy Pitchappan 5 , CG Nicholas Mascie-Taylor 1 , Lalji  Singh 4,6 , Marta Mirazon-Lahr 7 , Mait Metspalu 2,3 , Kumarasamy Thangaraj 4 , Toomas Kivisild 1,3 1 Division of Biological Anthropology, University of Cambridge, Cambridge, UK,  2 Evolutionary Biology Group, Estonian  Biocentre, Tartu, Estonia,  3 Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia,  4 Centre for Cellular  and Molecular Biology, Hyderabad, India,  5 Chettinad Academy of Research and Education, Chettinad Health City,  Chennai, India,  6 Banaras Hindu University, Varanasi, India,  7 Leverhulme Centre for Human Evolutionary Studies,  Division of Biological Anthropology, University of Cambridge, Cambridge, UK  

Human skin colour is a polygenic trait that is primarily determined by the amount and type of melanin produced in the  skin. The pigmentation variation between human populations across the world is highly correlated with geographic  latitude and the amount of UV radiation. Association studies together with research involving different model organisms  and coat colour variation have largely contributed to the identification of more than 378 pigmentation candidate genes.  These include TYR OCA2, that are known to cause albinism, MC1R responsible for the red hair phenotype, and genes  such as MATP, SLC24A5 and ASIP that are involved in normal pigmentation variation. In particular, SLC24A5 has been  shown to explain one third of the pigmentation difference between Europeans and Africans. However, the same gene  cannot explain the lighter East Asian phenotype; therefore, light pigmentation could be the result of convergent  evolution. A study on UK residents of Pakistani, Indian and Bangladeshi descent found significant association of  SLC24A5, SLC45A2 and TYR genes with skin colour. While these genes may explain a significant proportion of  interethnic differences in skin colour, it is not clear how much variation such genes explain within Indian populations  who are known for their high level of diversity of pigmentation. We have tested 15 candidate SNPs for association with  melanin index in a large sample of 1300 individuals, from three related castes native to South India. Using logistic  regression model we found that SLC24A5 functional SNP, rs1426654, is strongly associated with pigmentation in our  sample and explains alone more than half of the skin colour difference between the light and the dark group of  individuals. Conversely, the other tested SNPs fail to show any significance; this strongly argues in favour of one gene  having a major effect on skin pigmentation within ethnic groups of South India, with other genes having small additional  effects on this trait. We genotyped the SLC24A5 variant in over 40 populations across India and found that latitudinal  differences alone cannot explain its frequency patterns in the subcontinent. Key questions arising from this research are  when and where did the light skin variant enter South Asia and the manner and reason for it spreading across the Indian  sub-continent. Hence, a comprehensive view of skin colour evolution requires that in depth sequence information be  corroborated with population (genetic) history and with ancient DNA data of past populations of Eurasia.