TY - JOUR

T1 - Genomic evidence of local adaptation to climate and diet in indigenous Siberians

AU - Hallmark, Brian

AU - Karafet, Tatiana M.

AU - Hsieh, Ping Hsun

AU - Osipova, Ludmila P.

AU - Watkins, Joseph C.

AU - Hammer, Michael F.

N1 - Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide single nucleotide polymorphism array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, and ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.

AB - The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide single nucleotide polymorphism array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, and ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.

KW - Brown adipose tissue

KW - Cold adaptation

KW - Diet

KW - Missense variant

KW - Natural selection

KW - Siberians

KW - Angiopoietin-like Proteins/genetics

KW - Haplotypes

KW - Group II Phospholipases A2/genetics

KW - Peptide Hormones/genetics

KW - Climate

KW - Gene Frequency

KW - Humans

KW - Selection, Genetic

KW - Adaptation, Biological

KW - Mutation, Missense

KW - Linkage Disequilibrium

KW - Perilipin-1/genetics

KW - Siberia

KW - Polymorphism, Single Nucleotide

KW - Genome, Human

KW - Evolution, Molecular

KW - LACTASE PERSISTENCE

KW - natural selection

KW - BROWN ADIPOSE-TISSUE

KW - POSITIVE SELECTION

KW - BASAL METABOLIC-RATES

KW - SECRETORY PHOSPHOLIPASE A(2)

KW - diet

KW - CLASSIC SELECTIVE SWEEPS

KW - THYROID-HORMONE

KW - missense variant

KW - cold adaptation

KW - brown adipose tissue

KW - NATURAL-SELECTION

KW - YAKUT SAKHA

KW - ANGIOPOIETIN-LIKE PROTEIN

UR - http://www.scopus.com/inward/record.url?scp=85061478089&partnerID=8YFLogxK

U2 - 10.1093/molbev/msy211

DO - 10.1093/molbev/msy211

M3 - Article

C2 - 30428071

AN - SCOPUS:85061478089

VL - 36

SP - 315

EP - 327

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 2

ER -