Mait Metspalu - Academia.edu (original) (raw)

Papers by Mait Metspalu

PLOS Genetics, 2015

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic language... more The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghani-stan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language's expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area

Proceedings of the …, Jan 1, 2009

Nucleic Acids and Molecular Biology, 2006

Nucleic Acids and Molecular Biology, 2006

What makes DNA attractive for those interested in questions about human evolutionary history is i... more What makes DNA attractive for those interested in questions about human evolutionary history is its inherent nature to reproduce itself imperfectly. After all, it was Darwin who pointed out that if there were no variation evo-lution would have been impossible. After the maternal ...

PLOS ONE, 2015

The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid diver... more The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid divergence as a result of the spatial expansion of its speakers from Central-East Europe, in early medieval times. This expansion-mainly to East Europe and the northern Balkans-resulted in the incorporation of genetic components from numerous autochthonous populations into the Slavic gene pools. Here, we characterize genetic variation in all extant ethnic groups speaking Balto-Slavic languages by analyzing mitochondrial DNA (n = 6,876), Y-chromosomes (n = 6,079) and genome-wide SNP profiles (n = 296), within PLOS ONE |

Science (New York, N.Y.), Jan 6, 2015

In order to explore the diversity and selective signatures of duplication and deletion human copy... more In order to explore the diversity and selective signatures of duplication and deletion human copy number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single nucleotide variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

Science (New York, N.Y.), Jan 21, 2015

How and when the Americas were populated remains contentious. Using ancient and modern genome-wid... more How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Following their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 KYA, one that is now dispersed across North and South America and the other is restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative…

by Mirosław Furmanek, Jan Kolář, Viktória Kiss, Karl-Göran Sjögren, Paul R. Duffy, Kristian Kristiansen, Andrey Epimakhov, Karin M Frei, Andrey Epimakhov, Vajk Szeverényi, Dalia Pokutta, Tamás Hajdu, Vasilii Soenov, Niels Lynnerup, Justyna Baron, Synaru Trifanova, Łukasz Pospieszny, Levon Yepiskoposyan, Aivar Kriiska, György Pálfi, Natalia Shishlina, Magdolna Vicze, Liivi Varul, Mait Metspalu, Peter Damgaard, Radosław Jarysz, and Cristina Longhi

The Bronze Age of Eurasia (c. 3,000-1,000 years BC) was a period of major cultural ... more The Bronze Age of Eurasia (c. 3,000-1,000 years BC) was a period of major cultural changes accompanying the transition from hunting-gathering and farming into early urban civilization. It remains debated how these transitions shaped the distribution of the human populations. To investigate this we used new methodological improvements to sequence low coverage genomes from 101 ancient humans from across Eurasia, covering the entire Bronze Age including the late Neolithic and the Iron Age. We show that around 3,000 BC, Europe and Central Asia receive a major genetic input from the Pontic-Caspian Steppe through people related to the Yamnaya culture, resulting in the formation of the Corded Ware Culture in Europe and the Afanasievo Culture in Central Asia. A thousand years later, migrations from Europe into Central Asia, gives rise to the Sintashta and Andronovo Cultures. During later Bronze Age, the European-derived populations in Asia are gradually replaced by multi-ethnic cultures.

PLoS ONE, 2006

The issue of errors in genetic data sets is of growing concern, particularly in population geneti... more The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently underexploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups ,30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity.

Human biology, 2013

The origin and history of the Ashkenazi Jewish population have long been of great interest, and a... more The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been ...

Background: Recent advances in the understanding of the maternal and paternal heritage of south a... more 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.

The American Journal of Human Genetics, 2014

Arctic populations live in an environment characterized by extreme cold and the absence of plant ... more Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6-23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.

Science, 2014

The New World Arctic, the last region of the Americas to be populated by humans, has a relatively... more The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.

Vertebrate Paleobiology and Paleoanthropology Series, 2007

... ee TOOMAS KIVISILD Leverhulme Centre for Human Evolutionary Studies Henry Wellcome Building F... more ... ee TOOMAS KIVISILD Leverhulme Centre for Human Evolutionary Studies Henry Wellcome Building Fitzwilliam Street University of Cambridge Cambridge CB2 1QH England t.kivisild@human-evol.cam.ac.uk Introduction Evidence ...

Nucleic Acids and Molecular Biology, 2006

PLOS Genetics, 2015

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic language... more The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghani-stan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language's expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area

Proceedings of the …, Jan 1, 2009

Nucleic Acids and Molecular Biology, 2006

Nucleic Acids and Molecular Biology, 2006

What makes DNA attractive for those interested in questions about human evolutionary history is i... more What makes DNA attractive for those interested in questions about human evolutionary history is its inherent nature to reproduce itself imperfectly. After all, it was Darwin who pointed out that if there were no variation evo-lution would have been impossible. After the maternal ...

PLOS ONE, 2015

The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid diver... more The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid divergence as a result of the spatial expansion of its speakers from Central-East Europe, in early medieval times. This expansion-mainly to East Europe and the northern Balkans-resulted in the incorporation of genetic components from numerous autochthonous populations into the Slavic gene pools. Here, we characterize genetic variation in all extant ethnic groups speaking Balto-Slavic languages by analyzing mitochondrial DNA (n = 6,876), Y-chromosomes (n = 6,079) and genome-wide SNP profiles (n = 296), within PLOS ONE |

Science (New York, N.Y.), Jan 6, 2015

In order to explore the diversity and selective signatures of duplication and deletion human copy... more In order to explore the diversity and selective signatures of duplication and deletion human copy number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single nucleotide variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

Science (New York, N.Y.), Jan 21, 2015

How and when the Americas were populated remains contentious. Using ancient and modern genome-wid... more How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Following their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 KYA, one that is now dispersed across North and South America and the other is restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative…

by Mirosław Furmanek, Jan Kolář, Viktória Kiss, Karl-Göran Sjögren, Paul R. Duffy, Kristian Kristiansen, Andrey Epimakhov, Karin M Frei, Andrey Epimakhov, Vajk Szeverényi, Dalia Pokutta, Tamás Hajdu, Vasilii Soenov, Niels Lynnerup, Justyna Baron, Synaru Trifanova, Łukasz Pospieszny, Levon Yepiskoposyan, Aivar Kriiska, György Pálfi, Natalia Shishlina, Magdolna Vicze, Liivi Varul, Mait Metspalu, Peter Damgaard, Radosław Jarysz, and Cristina Longhi

The Bronze Age of Eurasia (c. 3,000-1,000 years BC) was a period of major cultural ... more The Bronze Age of Eurasia (c. 3,000-1,000 years BC) was a period of major cultural changes accompanying the transition from hunting-gathering and farming into early urban civilization. It remains debated how these transitions shaped the distribution of the human populations. To investigate this we used new methodological improvements to sequence low coverage genomes from 101 ancient humans from across Eurasia, covering the entire Bronze Age including the late Neolithic and the Iron Age. We show that around 3,000 BC, Europe and Central Asia receive a major genetic input from the Pontic-Caspian Steppe through people related to the Yamnaya culture, resulting in the formation of the Corded Ware Culture in Europe and the Afanasievo Culture in Central Asia. A thousand years later, migrations from Europe into Central Asia, gives rise to the Sintashta and Andronovo Cultures. During later Bronze Age, the European-derived populations in Asia are gradually replaced by multi-ethnic cultures.

PLoS ONE, 2006

The issue of errors in genetic data sets is of growing concern, particularly in population geneti... more The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently underexploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups ,30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity.

Human biology, 2013

The origin and history of the Ashkenazi Jewish population have long been of great interest, and a... more The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ~1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been ...

Background: Recent advances in the understanding of the maternal and paternal heritage of south a... more 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.

The American Journal of Human Genetics, 2014

Arctic populations live in an environment characterized by extreme cold and the absence of plant ... more Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6-23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.

Science, 2014

The New World Arctic, the last region of the Americas to be populated by humans, has a relatively... more The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.

Vertebrate Paleobiology and Paleoanthropology Series, 2007

... ee TOOMAS KIVISILD Leverhulme Centre for Human Evolutionary Studies Henry Wellcome Building F... more ... ee TOOMAS KIVISILD Leverhulme Centre for Human Evolutionary Studies Henry Wellcome Building Fitzwilliam Street University of Cambridge Cambridge CB2 1QH England t.kivisild@human-evol.cam.ac.uk Introduction Evidence ...

Nucleic Acids and Molecular Biology, 2006