TY - JOUR

T1 - Exome Sequencing Provides Evidence of Polygenic Adaptation to a Fat-Rich Animal Diet in Indigenous Siberian Populations

AU - Hsieh, Ping Hsun

AU - Hallmark, Brian

AU - Watkins, Joseph

AU - Karafet, Tatiana M.

AU - Osipova, Ludmila P.

AU - Gutenkunst, Ryan N.

AU - Hammer, Michael F.

N1 - © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Siberia is one of the coldest environments on Earth and has great seasonal temperature variation. Long-term settlement in northern Siberia undoubtedly required biological adaptation to severe cold stress, dramatic variation in photoperiod, and limited food resources. In addition, recent archeological studies show that humans first occupied Siberia at least 45,000 years ago; yet our understanding of the demographic history of modern indigenous Siberians remains incomplete. In this study, we use whole-exome sequencing data from the Nganasans and Yakuts to infer the evolutionary history of these two indigenous Siberian populations. Recognizing the complexity of the adaptive process, we designed a model-based test to systematically search for signatures of polygenic selection. Our approach accounts for stochasticity in the demographic process and the hitchhiking effect of classic selective sweeps, as well as potential biases resulting from recombination rate and mutation rate heterogeneity. Our demographic inference shows that the Nganasans and Yakuts diverged ∼12,000-13,000 years ago from East-Asian ancestors in a process involving continuous gene flow. Our polygenic selection scan identifies seven candidate gene sets with Siberian-specific signals. Three of these gene sets are related to diet, especially to fat metabolism, consistent with the hypothesis of adaptation to a fat-rich animal diet. Additional testing rejects the effect of hitchhiking and favors a model in which selection yields small allele frequency changes at multiple unlinked genes.

AB - Siberia is one of the coldest environments on Earth and has great seasonal temperature variation. Long-term settlement in northern Siberia undoubtedly required biological adaptation to severe cold stress, dramatic variation in photoperiod, and limited food resources. In addition, recent archeological studies show that humans first occupied Siberia at least 45,000 years ago; yet our understanding of the demographic history of modern indigenous Siberians remains incomplete. In this study, we use whole-exome sequencing data from the Nganasans and Yakuts to infer the evolutionary history of these two indigenous Siberian populations. Recognizing the complexity of the adaptive process, we designed a model-based test to systematically search for signatures of polygenic selection. Our approach accounts for stochasticity in the demographic process and the hitchhiking effect of classic selective sweeps, as well as potential biases resulting from recombination rate and mutation rate heterogeneity. Our demographic inference shows that the Nganasans and Yakuts diverged ∼12,000-13,000 years ago from East-Asian ancestors in a process involving continuous gene flow. Our polygenic selection scan identifies seven candidate gene sets with Siberian-specific signals. Three of these gene sets are related to diet, especially to fat metabolism, consistent with the hypothesis of adaptation to a fat-rich animal diet. Additional testing rejects the effect of hitchhiking and favors a model in which selection yields small allele frequency changes at multiple unlinked genes.

KW - adaptation

KW - diet

KW - extreme climates

KW - polygenic selection

KW - Siberia

KW - Extreme climates

KW - Diet

KW - Polygenic selection

KW - Adaptation

KW - DNA, Mitochondrial/genetics

KW - Humans

KW - Phylogeny

KW - Genetic Variation/genetics

KW - Gene Flow/genetics

KW - Asian Continental Ancestry Group/genetics

KW - Dietary Fats

KW - Exome/genetics

KW - Acclimatization/genetics

KW - Adaptation, Biological/genetics

KW - Demography/methods

KW - Multifactorial Inheritance/genetics

KW - Gene Frequency/genetics

KW - Whole Exome Sequencing/methods

KW - Biological Evolution

KW - Ethnic Groups/genetics

KW - Alleles

KW - Genetics, Population/methods

KW - DEMOGRAPHIC INFERENCE

KW - MUTATION-RATE

KW - HIGH-ALTITUDE

KW - ACID-METABOLISM

KW - HUMAN-EVOLUTION

KW - HUNTER-GATHERER

KW - GENOME SEQUENCE

KW - GENETIC-VARIATION

KW - NATURAL-SELECTION

KW - HISTORY

UR - http://www.scopus.com/inward/record.url?scp=85044162688&partnerID=8YFLogxK

U2 - 10.1093/molbev/msx226

DO - 10.1093/molbev/msx226

M3 - Article

C2 - 28962010

AN - SCOPUS:85044162688

VL - 34

SP - 2913

EP - 2926

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 11

ER -