Genome-Wide Analysis of Cold Adaptation in Indigenous Siberian Populations

Abstract

Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels and increased blood pressure that have been attributed to adaptation to the extreme cold climate. In this study we introduce a dataset of 200 individuals from ten indigenous Siberian populations that were genotyped for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. A region on chromosome 11 (chr11:66–69 Mb) contained the largest amount of clustering of significant signals and also the strongest signals in all the different selection tests performed. We present a list of candidate cold adaption genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture.

Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes

“…However, of the traits tested (ESM Tables 4, 5), no clear POE was observed. Interestingly, a recent study showed THADA to be one of the strongest signals for cold adaptation [40], but such phenotypes were not available in the trios.…”

The Evolutionary Origin and Genetic Makeup of Domestic Horses

“…Interestingly, the biological significance of some of these candidates was corroborated in woolly mammoths (Lynch et al 2015), where parallel episodes of positive selection have been described at the BARX2 and PHIP genes, associated with hair development and insulin metabolism, respectively. Similarly, human groups from Siberia (Cardona et al 2014) also show adaptive footprints at the PRKG1 gene, which participates in shivering by regulating blood vessel constriction. Altogether, such patterns of convergent evolution support regulatory changes as a key mechanism for driving rapid adaptive processes, mainly because these regions offer an important fraction of the segregating variation readily available for natural selection.…”

Genetic signature of natural selection in first Americans

“…2 and Table S3). Cardona et al (24) surveyed the entirety of Siberian chromosome 11 and found no indication of selection at the FADS region. Therefore, the presence of the putatively selected FADS haplotype might have resulted from subsequent gene flow between Native Americans and Siberian populations occurring after the Beringian event.…”