The selection landscape and genetic legacy of ancient Eurasians

Evan K Irving-Pease; Alba Refoyo-Martínez; William Barrie; Andrés Ingason; Alice Pearson; Anders Fischer; Karl-Göran Sjögren; Alma S Halgren; Ruairidh Macleod; Fabrice Demeter; Rasmus A Henriksen; Tharsika Vimala; Hugh McColl; Andrew H Vaughn; Leo Speidel; Aaron J Stern; Gabriele Scorrano; Abigail Ramsøe; Andrew J Schork; Anders Rosengren; Lei Zhao; Kristian Kristiansen; Astrid K N Iversen; Lars Fugger; Peter H Sudmant; Daniel J Lawson; Richard Durbin; Thorfinn Korneliussen; Thomas Werge; Morten E Allentoft; Martin Sikora; Rasmus Nielsen; Fernando Racimo; Eske Willerslev

doi:10.1038/s41586-023-06705-1

The selection landscape and genetic legacy of ancient Eurasians

Evan K Irving-Pease^*, Alba Refoyo-Martínez, William Barrie, Andrés Ingason, Alice Pearson, Anders Fischer, Karl-Göran Sjögren, Alma S Halgren, Ruairidh Macleod, Fabrice Demeter, Rasmus A Henriksen, Tharsika Vimala, Hugh McColl, Andrew H Vaughn, Leo Speidel, Aaron J Stern, Gabriele Scorrano, Abigail Ramsøe, Andrew J Schork, Anders RosengrenLei Zhao, Kristian Kristiansen, Astrid K N Iversen, Lars Fugger, Peter H Sudmant, Daniel J Lawson, Richard Durbin, Thorfinn Korneliussen, Thomas Werge, Morten E Allentoft, Martin Sikora, Rasmus Nielsen, Fernando Racimo, Eske Willerslev

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

36 Citations (Scopus)

Abstract

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Original language	English
Pages (from-to)	312–320
Number of pages	9
Journal	Nature
Volume	625
DOIs	https://doi.org/10.1038/s41586-023-06705-1 https://doi.org/10.1038/s41586-023-06705-1 https://doi.org/10.1101/2022.09.22.509027
Publication status	Published - 10 Jan 2024

Bibliographical note

Funding Information:
We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John’s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K.. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union’s Horizon Europe programme (grant agreements No. 101077592 and 951385).

Funding Information:
We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John’s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union’s Horizon Europe programme (grant agreements No. 101077592 and 951385).

Publisher Copyright:
© 2024, The Author(s).

Keywords

Humans
Affect
Agriculture/history
Alleles
Alzheimer Disease/genetics
Asia/ethnology
Asian/genetics
Diabetes Mellitus/genetics
Europe/ethnology
European People/genetics
Farmers/history
Genetic Loci/genetics
Genetic Predisposition to Disease
Genome, Human/genetics
History, Ancient
Human Migration
Hunting/history
Multigene Family/genetics
Phenotype
Selection, Genetic
UK Biobank
Multifactorial Inheritance/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Irving-Pease, E. K., Refoyo-Martínez, A., Barrie, W., Ingason, A., Pearson, A., Fischer, A., Sjögren, K.-G., Halgren, A. S., Macleod, R., Demeter, F., Henriksen, R. A., Vimala, T., McColl, H., Vaughn, A. H., Speidel, L., Stern, A. J., Scorrano, G., Ramsøe, A., Schork, A. J., ... Willerslev, E. (2024). The selection landscape and genetic legacy of ancient Eurasians. Nature, 625, 312–320. https://doi.org/10.1038/s41586-023-06705-1, https://doi.org/10.1038/s41586-023-06705-1, https://doi.org/10.1101/2022.09.22.509027

@article{121eba7fed6a4b649ebc2c292c7824f0,

title = "The selection landscape and genetic legacy of ancient Eurasians",

abstract = "The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer{\textquoteright}s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.",

keywords = "Humans, Affect, Agriculture/history, Alleles, Alzheimer Disease/genetics, Asia/ethnology, Asian/genetics, Diabetes Mellitus/genetics, Europe/ethnology, European People/genetics, Farmers/history, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome, Human/genetics, History, Ancient, Human Migration, Hunting/history, Multigene Family/genetics, Phenotype, Selection, Genetic, UK Biobank, Multifactorial Inheritance/genetics",

author = "Irving-Pease, \{Evan K\} and Alba Refoyo-Mart{\'i}nez and William Barrie and Andr{\'e}s Ingason and Alice Pearson and Anders Fischer and Karl-G{\"o}ran Sj{\"o}gren and Halgren, \{Alma S\} and Ruairidh Macleod and Fabrice Demeter and Henriksen, \{Rasmus A\} and Tharsika Vimala and Hugh McColl and Vaughn, \{Andrew H\} and Leo Speidel and Stern, \{Aaron J\} and Gabriele Scorrano and Abigail Rams{\o}e and Schork, \{Andrew J\} and Anders Rosengren and Lei Zhao and Kristian Kristiansen and Iversen, \{Astrid K N\} and Lars Fugger and Sudmant, \{Peter H\} and Lawson, \{Daniel J\} and Richard Durbin and Thorfinn Korneliussen and Thomas Werge and Allentoft, \{Morten E\} and Martin Sikora and Rasmus Nielsen and Fernando Racimo and Eske Willerslev",

note = "Funding Information: We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John{\textquoteright}s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K.. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon Europe programme (grant agreements No. 101077592 and 951385). Funding Information: We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John{\textquoteright}s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon Europe programme (grant agreements No. 101077592 and 951385). Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = jan,

day = "10",

doi = "10.1038/s41586-023-06705-1",

language = "English",

volume = "625",

pages = "312–320",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

}

Irving-Pease, EK, Refoyo-Martínez, A, Barrie, W, Ingason, A, Pearson, A, Fischer, A, Sjögren, K-G, Halgren, AS, Macleod, R, Demeter, F, Henriksen, RA, Vimala, T, McColl, H, Vaughn, AH, Speidel, L, Stern, AJ, Scorrano, G, Ramsøe, A, Schork, AJ, Rosengren, A, Zhao, L, Kristiansen, K, Iversen, AKN, Fugger, L, Sudmant, PH, Lawson, DJ, Durbin, R, Korneliussen, T, Werge, T, Allentoft, ME, Sikora, M, Nielsen, R, Racimo, F & Willerslev, E 2024, 'The selection landscape and genetic legacy of ancient Eurasians', Nature, vol. 625, pp. 312–320. https://doi.org/10.1038/s41586-023-06705-1, https://doi.org/10.1038/s41586-023-06705-1, https://doi.org/10.1101/2022.09.22.509027

TY - JOUR

T1 - The selection landscape and genetic legacy of ancient Eurasians

AU - Irving-Pease, Evan K

AU - Refoyo-Martínez, Alba

AU - Barrie, William

AU - Ingason, Andrés

AU - Pearson, Alice

AU - Fischer, Anders

AU - Sjögren, Karl-Göran

AU - Halgren, Alma S

AU - Macleod, Ruairidh

AU - Demeter, Fabrice

AU - Henriksen, Rasmus A

AU - Vimala, Tharsika

AU - McColl, Hugh

AU - Vaughn, Andrew H

AU - Speidel, Leo

AU - Stern, Aaron J

AU - Scorrano, Gabriele

AU - Ramsøe, Abigail

AU - Schork, Andrew J

AU - Rosengren, Anders

AU - Zhao, Lei

AU - Kristiansen, Kristian

AU - Iversen, Astrid K N

AU - Fugger, Lars

AU - Sudmant, Peter H

AU - Lawson, Daniel J

AU - Durbin, Richard

AU - Korneliussen, Thorfinn

AU - Werge, Thomas

AU - Allentoft, Morten E

AU - Sikora, Martin

AU - Nielsen, Rasmus

AU - Racimo, Fernando

AU - Willerslev, Eske

N1 - Funding Information: We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John’s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K.. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union’s Horizon Europe programme (grant agreements No. 101077592 and 951385). Funding Information: We thank all the former and current staff at the Lundbeck Foundation GeoGenetics Centre and the GeoGenetics Sequencing Core and colleagues across the many institutions detailed below. We are particularly grateful to L. Olsen as project manager for the Lundbeck Foundation GeoGenetics Centre project. We thank UKB for access to the UKB genomic resource. We want to acknowledge the participants and investigators of the FinnGen study. We are thankful to Illumina for collaboration. E.W. thanks St. John’s College, Cambridge, for providing a stimulating environment of discussion and learning. The Lundbeck Foundation GeoGenetics Centre is supported by the Lundbeck Foundation (R302-2018-2155 and R155-2013-16338), the Novo Nordisk Foundation (NNF18SA0035006), the Wellcome Trust (214300), Carlsberg Foundation (CF18-0024), the Danish National Research Foundation (DNRF94 and DNRF174), the University of Copenhagen (KU2016 programme), Ferring Pharmaceuticals A/S and a COREX ERC Synergy grant (ID 951385). This research has been conducted using the UKB Resource and the iPSYCH Initiative, funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724). This work was further supported by the Swedish Foundation for Humanities and Social Sciences grant (Riksbankens Jubileumsfond M16-0455:1) to K.K. E.K.I.-P. and A.R.-M. were supported by the Lundbeck Foundation (R302-2018-2155) and the Novo Nordisk Foundation (NNF18SA0035006). A.P., R.D. and E.W. were supported by the Wellcome Trust (214300). R.M. was supported by a SSHRC doctoral studentship (G101449). R.A.H. and T.K. were supported by the Carlsberg Foundation (CF19-0712). L.S. was supported by a Sir Henry Wellcome fellowship (220457/Z/20/Z). L.F. was supported by the OAK Foundation (OCAY-15-520). P.H.S. was supported by the Institute of General Medical Sciences (R35GM142916) and a Vallee Scholars Award. R.N. was supported by the National Institutes of Health (R01GM138634). F.R. was supported by a Villum Young Investigator Grant (project no. 00025300), a Novo Nordisk Fonden Data Science Ascending Investigator Award (NNF22OC0076816) and by the European Research Council (ERC) under the European Union’s Horizon Europe programme (grant agreements No. 101077592 and 951385). Publisher Copyright: © 2024, The Author(s).

PY - 2024/1/10

Y1 - 2024/1/10

N2 - The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

AB - The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

KW - Humans

KW - Affect

KW - Agriculture/history

KW - Alleles

KW - Alzheimer Disease/genetics

KW - Asia/ethnology

KW - Asian/genetics

KW - Diabetes Mellitus/genetics

KW - Europe/ethnology

KW - European People/genetics

KW - Farmers/history

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease

KW - Genome, Human/genetics

KW - History, Ancient

KW - Human Migration

KW - Hunting/history

KW - Multigene Family/genetics

KW - Phenotype

KW - Selection, Genetic

KW - UK Biobank

KW - Multifactorial Inheritance/genetics

U2 - 10.1038/s41586-023-06705-1

DO - 10.1038/s41586-023-06705-1

M3 - Article (Academic Journal)

C2 - 38200293

SN - 0028-0836

VL - 625

SP - 312

EP - 320

JO - Nature

JF - Nature

ER -

The selection landscape and genetic legacy of ancient Eurasians

Abstract

Bibliographical note

Keywords

UN SDGs

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