Publications by authors named "Georgi Hudjashov"

22 Publications

  • Page 1 of 1

Widespread Denisovan ancestry in Island Southeast Asia but no evidence of substantial super-archaic hominin admixture.

Nat Ecol Evol 2021 05 22;5(5):616-624. Epub 2021 Mar 22.

ARC Centre of Excellence for Australian Biodiversity and Heritage (CABAH), University of New South Wales, Sydney, New South Wales, Australia.

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic 'super-archaic' species-Homo luzonensis and H. floresiensis-were present around the time anatomically modern humans arrived in the region >50,000 years ago. Intriguingly, contemporary human populations across ISEA carry distinct genomic traces of ancient interbreeding events with Denisovans-a separate hominin lineage that currently lacks a fossil record in ISEA. To query this apparent disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes, including >200 from ISEA. Our results corroborate widespread Denisovan ancestry in ISEA populations, but fail to detect any substantial super-archaic admixture signals compatible with the endemic fossil record of ISEA. We discuss the implications of our findings for the understanding of hominin history in ISEA, including future research directions that might help to unlock more details about the prehistory of the enigmatic Denisovans.
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http://dx.doi.org/10.1038/s41559-021-01408-0DOI Listing
May 2021

Differences in local population history at the finest level: the case of the Estonian population.

Eur J Hum Genet 2020 11 25;28(11):1580-1591. Epub 2020 Jul 25.

Estonian Biocentre, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia.

Several recent studies detected fine-scale genetic structure in human populations. Hence, groups conventionally treated as single populations harbour significant variation in terms of allele frequencies and patterns of haplotype sharing. It has been shown that these findings should be considered when performing studies of genetic associations and natural selection, especially when dealing with polygenic phenotypes. However, there is little understanding of the practical effects of such genetic structure on demography reconstructions and selection scans when focusing on recent population history. Here we tested the impact of population structure on such inferences using high-coverage (~30×) genome sequences of 2305 Estonians. We show that different regions of Estonia differ in both effective population size dynamics and signatures of natural selection. By analyzing identity-by-descent segments we also reveal that some Estonian regions exhibit evidence of a bottleneck 10-15 generations ago reflecting sequential episodes of wars, plague and famine, although this signal is virtually undetected when treating Estonia as a single population. Besides that, we provide a framework for relating effective population size estimated from genetic data to actual census size and validate it on the Estonian population. This approach may be widely used both to cross-check estimates based on historical sources as well as to get insight into times and/or regions with no other information available. Our results suggest that the history of human populations within the last few millennia can be highly region specific and cannot be properly studied without taking local genetic structure into account.
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http://dx.doi.org/10.1038/s41431-020-0699-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575549PMC
November 2020

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago.

PLoS Genet 2020 05 26;16(5):e1008749. Epub 2020 May 26.

Melbourne Integrative Genomics, University of Melbourne, Parkville, Australia.

Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia's tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by fine-scale environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.
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http://dx.doi.org/10.1371/journal.pgen.1008749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274483PMC
May 2020

Correction to: Archaic mitochondrial DNA inserts in modern day nuclear genomes.

BMC Genomics 2020 01 17;21(1):55. Epub 2020 Jan 17.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D04103, Leipzig, Germany.

Following the publication of this article [1], the authors reported that the captions of Figs. 3 and 4 were published in the incorrect order, whereby they mismatch with their corresponding images.
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http://dx.doi.org/10.1186/s12864-020-6449-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966873PMC
January 2020

Archaic mitochondrial DNA inserts in modern day nuclear genomes.

BMC Genomics 2019 Dec 26;20(1):1017. Epub 2019 Dec 26.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, D04103, Germany.

Background: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs).

Results: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male.

Conclusions: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.
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http://dx.doi.org/10.1186/s12864-019-6392-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933719PMC
December 2019

Multiple Deeply Divergent Denisovan Ancestries in Papuans.

Cell 2019 05 11;177(4):1010-1021.e32. Epub 2019 Apr 11.

Statistics and Bioinformatics Group, School of Fundamental Sciences, Massey University, Palmerston North 4410, New Zealand. Electronic address:

Genome sequences are known for two archaic hominins-Neanderthals and Denisovans-which interbred with anatomically modern humans as they dispersed out of Africa. We identified high-confidence archaic haplotypes in 161 new genomes spanning 14 island groups in Island Southeast Asia and New Guinea and found large stretches of DNA that are inconsistent with a single introgressing Denisovan origin. Instead, modern Papuans carry hundreds of gene variants from two deeply divergent Denisovan lineages that separated over 350 thousand years ago. Spatial and temporal structure among these lineages suggest that introgression from one of these Denisovan groups predominantly took place east of the Wallace line and continued until near the end of the Pleistocene. A third Denisovan lineage occurs in modern East Asians. This regional mosaic suggests considerable complexity in archaic contact, with modern humans interbreeding with multiple Denisovan groups that were geographically isolated from each other over deep evolutionary time.
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http://dx.doi.org/10.1016/j.cell.2019.02.035DOI Listing
May 2019

Genes reveal traces of common recent demographic history for most of the Uralic-speaking populations.

Genome Biol 2018 09 21;19(1):139. Epub 2018 Sep 21.

Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478, Russia.

Background: The genetic origins of Uralic speakers from across a vast territory in the temperate zone of North Eurasia have remained elusive. Previous studies have shown contrasting proportions of Eastern and Western Eurasian ancestry in their mitochondrial and Y chromosomal gene pools. While the maternal lineages reflect by and large the geographic background of a given Uralic-speaking population, the frequency of Y chromosomes of Eastern Eurasian origin is distinctively high among European Uralic speakers. The autosomal variation of Uralic speakers, however, has not yet been studied comprehensively.

Results: Here, we present a genome-wide analysis of 15 Uralic-speaking populations which cover all main groups of the linguistic family. We show that contemporary Uralic speakers are genetically very similar to their local geographical neighbours. However, when studying relationships among geographically distant populations, we find that most of the Uralic speakers and some of their neighbours share a genetic component of possibly Siberian origin. Additionally, we show that most Uralic speakers share significantly more genomic segments identity-by-descent with each other than with geographically equidistant speakers of other languages. We find that correlated genome-wide genetic and lexical distances among Uralic speakers suggest co-dispersion of genes and languages. Yet, we do not find long-range genetic ties between Estonians and Hungarians with their linguistic sisters that would distinguish them from their non-Uralic-speaking neighbours.

Conclusions: We show that most Uralic speakers share a distinct ancestry component of likely Siberian origin, which suggests that the spread of Uralic languages involved at least some demic component.
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http://dx.doi.org/10.1186/s13059-018-1522-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151024PMC
September 2018

Investigating the origins of eastern Polynesians using genome-wide data from the Leeward Society Isles.

Sci Rep 2018 01 29;8(1):1823. Epub 2018 Jan 29.

Department of Molecular Biology, Colorado College, Colorado Springs, Colorado, 80903, USA.

The debate concerning the origin of the Polynesian speaking peoples has been recently reinvigorated by genetic evidence for secondary migrations to western Polynesia from the New Guinea region during the 2nd millennium BP. Using genome-wide autosomal data from the Leeward Society Islands, the ancient cultural hub of eastern Polynesia, we find that the inhabitants' genomes also demonstrate evidence of this episode of admixture, dating to 1,700-1,200 BP. This supports a late settlement chronology for eastern Polynesia, commencing ~1,000 BP, after the internal differentiation of Polynesian society. More than 70% of the autosomal ancestry of Leeward Society Islanders derives from Island Southeast Asia with the lowland populations of the Philippines as the single largest potential source. These long-distance migrants into Polynesia experienced additional admixture with northern Melanesians prior to the secondary migrations of the 2nd millennium BP. Moreover, the genetic diversity of mtDNA and Y chromosome lineages in the Leeward Society Islands is consistent with linguistic evidence for settlement of eastern Polynesia proceeding from the central northern Polynesian outliers in the Solomon Islands. These results stress the complex demographic history of the Leeward Society Islands and challenge phylogenetic models of cultural evolution predicated on eastern Polynesia being settled from Samoa.
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http://dx.doi.org/10.1038/s41598-018-20026-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789021PMC
January 2018

Evidence of Early-Stage Selection on EPAS1 and GPR126 Genes in Andean High Altitude Populations.

Sci Rep 2017 10 12;7(1):13042. Epub 2017 Oct 12.

Department of Archaeology and Anthropology, University of Cambridge, Cambridge, Cambridgeshire, UK.

The aim of this study is to identify genetic variants that harbour signatures of recent positive selection and may facilitate physiological adaptations to hypobaric hypoxia. To achieve this, we conducted whole genome sequencing and lung function tests in 19 Argentinean highlanders (>3500 m) comparing them to 16 Native American lowlanders. We developed a new statistical procedure using a combination of population branch statistics (PBS) and number of segregating sites by length (nSL) to detect beneficial alleles that arose since the settlement of the Andes and are currently present in 15-50% of the population. We identified two missense variants as significant targets of selection. One of these variants, located within the GPR126 gene, has been previously associated with the forced expiratory volume/forced vital capacity ratio. The other novel missense variant mapped to the EPAS1 gene encoding the hypoxia inducible factor 2α. EPAS1 is known to be the major selection candidate gene in Tibetans. The derived allele of GPR126 is associated with lung function in our sample of highlanders (p < 0.05). These variants may contribute to the physiological adaptations to hypobaric hypoxia, possibly by altering lung function. The new statistical approach might be a useful tool to detect selected variants in population studies.
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http://dx.doi.org/10.1038/s41598-017-13382-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638799PMC
October 2017

Complex Patterns of Admixture across the Indonesian Archipelago.

Mol Biol Evol 2017 10;34(10):2439-2452

Statistics and Bioinformatics Group, Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.

Indonesia, an island nation as large as continental Europe, hosts a sizeable proportion of global human diversity, yet remains surprisingly undercharacterized genetically. Here, we substantially expand on existing studies by reporting genome-scale data for nearly 500 individuals from 25 populations in Island Southeast Asia, New Guinea, and Oceania, notably including previously unsampled islands across the Indonesian archipelago. We use high-resolution analyses of haplotype diversity to reveal fine detail of regional admixture patterns, with a particular focus on the Holocene. We find that recent population history within Indonesia is complex, and that populations from the Philippines made important genetic contributions in the early phases of the Austronesian expansion. Different, but interrelated processes, acted in the east and west. The Austronesian migration took several centuries to spread across the eastern part of the archipelago, where genetic admixture postdates the archeological signal. As with the Neolithic expansion further east in Oceania and in Europe, genetic mixing with local inhabitants in eastern Indonesia lagged behind the arrival of farming populations. In contrast, western Indonesia has a more complicated admixture history shaped by interactions with mainland Asian and Austronesian newcomers, which for some populations occurred more than once. Another layer of complexity in the west was introduced by genetic contact with South Asia and strong demographic events in isolated local groups.
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http://dx.doi.org/10.1093/molbev/msx196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850824PMC
October 2017

Selective sweep on human amylase genes postdates the split with Neanderthals.

Sci Rep 2016 11 17;6:37198. Epub 2016 Nov 17.

Department of Archaeology and Anthropology, University of Cambridge, Cambridge, CB2 3QG, UK.

Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content.
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http://dx.doi.org/10.1038/srep37198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112570PMC
November 2016

Genomic analyses inform on migration events during the peopling of Eurasia.

Nature 2016 Oct 21;538(7624):238-242. Epub 2016 Sep 21.

Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.
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http://dx.doi.org/10.1038/nature19792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164938PMC
October 2016

Small Traditional Human Communities Sustain Genomic Diversity over Microgeographic Scales despite Linguistic Isolation.

Mol Biol Evol 2016 09 7;33(9):2273-84. Epub 2016 Jun 7.

Complexity Institute, Nanyang Technological University, Singapore.

At least since the Neolithic, humans have largely lived in networks of small, traditional communities. Often socially isolated, these groups evolved distinct languages and cultures over microgeographic scales of just tens of kilometers. Population genetic theory tells us that genetic drift should act quickly in such isolated groups, thus raising the question: do networks of small human communities maintain levels of genetic diversity over microgeographic scales? This question can no longer be asked in most parts of the world, which have been heavily impacted by historical events that make traditional society structures the exception. However, such studies remain possible in parts of Island Southeast Asia and Oceania, where traditional ways of life are still practiced. We captured genome-wide genetic data, together with linguistic records, for a case-study system-eight villages distributed across Sumba, a small, remote island in eastern Indonesia. More than 4,000 years after these communities were established during the Neolithic period, most speak different languages and can be distinguished genetically. Yet their nuclear diversity is not reduced, instead being comparable to other, even much larger, regional groups. Modeling reveals a separation of time scales: while languages and culture can evolve quickly, creating social barriers, sporadic migration averaged over many generations is sufficient to keep villages linked genetically. This loosely-connected network structure, once the global norm and still extant on Sumba today, provides a living proxy to explore fine-scale genome dynamics in the sort of small traditional communities within which the most recent episodes of human evolution occurred.
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http://dx.doi.org/10.1093/molbev/msw099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989104PMC
September 2016

A recent bottleneck of Y chromosome diversity coincides with a global change in culture.

Genome Res 2015 Apr 13;25(4):459-66. Epub 2015 Mar 13.

Center of Molecular Diagnosis and Genetic Research, University Hospital of Obstetrics and Gynecology, Tirana, ALB1005, Albania;

It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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http://dx.doi.org/10.1101/gr.186684.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381518PMC
April 2015

Evolution of the pygmy phenotype: evidence of positive selection fro genome-wide scans in African, Asian, and Melanesian pygmies.

Hum Biol 2013 Feb-Jun;85(1-3):251-84

Department of Anthropology, University College London, London, UK.

Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups.
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http://dx.doi.org/10.3378/027.085.0313DOI Listing
April 2015

The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent.

PLoS Genet 2013 Nov 7;9(11):e1003912. Epub 2013 Nov 7.

Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia ; Estonian Biocentre, Tartu, Estonia.

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.
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http://dx.doi.org/10.1371/journal.pgen.1003912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820762PMC
November 2013

Global patterns of diversity and selection in human tyrosinase gene.

PLoS One 2013 11;8(9):e74307. Epub 2013 Sep 11.

Evolutionary Biology Group, Estonian Biocentre, Tartu, Estonia ; Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074307PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770694PMC
June 2014

Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

Am J Hum Genet 2011 Dec;89(6):731-44

Evolutionary Biology Group, Estonian Biocentre, Tartu, Estonia.

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes.
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http://dx.doi.org/10.1016/j.ajhg.2011.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234374PMC
December 2011

Population genetic structure in Indian Austroasiatic speakers: the role of landscape barriers and sex-specific admixture.

Mol Biol Evol 2011 Feb 26;28(2):1013-24. Epub 2010 Oct 26.

Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu and Estonian Biocentre, Tartu, Estonia.

The geographic origin and time of dispersal of Austroasiatic (AA) speakers, presently settled in south and southeast Asia, remains disputed. Two rival hypotheses, both assuming a demic component to the language dispersal, have been proposed. The first of these places the origin of Austroasiatic speakers in southeast Asia with a later dispersal to south Asia during the Neolithic, whereas the second hypothesis advocates pre-Neolithic origins and dispersal of this language family from south Asia. To test the two alternative models, this study combines the analysis of uniparentally inherited markers with 610,000 common single nucleotide polymorphism loci from the nuclear genome. Indian AA speakers have high frequencies of Y chromosome haplogroup O2a; our results show that this haplogroup has significantly higher diversity and coalescent time (17-28 thousand years ago) in southeast Asia, strongly supporting the first of the two hypotheses. Nevertheless, the results of principal component and "structure-like" analyses on autosomal loci also show that the population history of AA speakers in India is more complex, being characterized by two ancestral components-one represented in the pattern of Y chromosomal and EDAR results and the other by mitochondrial DNA diversity and genomic structure. We propose that AA speakers in India today are derived from dispersal from southeast Asia, followed by extensive sex-specific admixture with local Indian populations.
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http://dx.doi.org/10.1093/molbev/msq288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355372PMC
February 2011

Climate change and postglacial human dispersals in southeast Asia.

Mol Biol Evol 2008 Jun 21;25(6):1209-18. Epub 2008 Mar 21.

Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region.
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http://dx.doi.org/10.1093/molbev/msn068DOI Listing
June 2008

Revealing the prehistoric settlement of Australia by Y chromosome and mtDNA analysis.

Proc Natl Acad Sci U S A 2007 May 11;104(21):8726-30. Epub 2007 May 11.

Estonian Biocentre and Tartu University, Department of Evolutionary Biology, Riia 23, 51010 Tartu, Estonia.

Published and new samples of Aboriginal Australians and Melanesians were analyzed for mtDNA (n=172) and Y variation (n=522), and the resulting profiles were compared with the branches known so far within the global mtDNA and the Y chromosome tree. (i) All Australian lineages are confirmed to fall within the mitochondrial founder branches M and N and the Y chromosomal founders C and F, which are associated with the exodus of modern humans from Africa approximately 50-70,000 years ago. The analysis reveals no evidence for any archaic maternal or paternal lineages in Australians, despite some suggestively robust features in the Australian fossil record, thus weakening the argument for continuity with any earlier Homo erectus populations in Southeast Asia. (ii) The tree of complete mtDNA sequences shows that Aboriginal Australians are most closely related to the autochthonous populations of New Guinea/Melanesia, indicating that prehistoric Australia and New Guinea were occupied initially by one and the same Palaeolithic colonization event approximately 50,000 years ago, in agreement with current archaeological evidence. (iii) The deep mtDNA and Y chromosomal branching patterns between Australia and most other populations around the Indian Ocean point to a considerable isolation after the initial arrival. (iv) We detect only minor secondary gene flow into Australia, and this could have taken place before the land bridge between Australia and New Guinea was submerged approximately 8,000 years ago, thus calling into question that certain significant developments in later Australian prehistory (the emergence of a backed-blade lithic industry, and the linguistic dichotomy) were externally motivated.
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http://dx.doi.org/10.1073/pnas.0702928104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885570PMC
May 2007

Most of the extant mtDNA boundaries in south and southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans.

BMC Genet 2004 Aug 31;5:26. Epub 2004 Aug 31.

Institute of Molecular and Cell Biology, Tartu University, Tartu, Estonia.

Background: Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia.

Results: Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades.

Conclusions: Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.
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http://dx.doi.org/10.1186/1471-2156-5-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC516768PMC
August 2004
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