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Testing natural selection on polygenic trait-associated alleles in anatolia using neolithic and present-day human genomes

Fer, Evrim
The Neolithic transition, which started approximately 10,000 year ago in west Eurasia and introduced sedentary life style and food production, led to major shifts in the human diet. Previous studies have reported strong selection signals on genes related to processing of plant-based diets (Buckley et al., 2017; Harris et al., 2019) or the consumption of dairy products (Schlebusch et al., 2013). With the advent of archeogenomics studies, genetic signatures of such adaptations have also been supported using DNA data from ancient populations (Mathieson et al., 2015). In this study, polygenic adaptations in Anatolia after the Neolithic transition were investigated by comparing Neolithic and modern-day genome sequence data. First, we chose 40 mainly polygenic traits previously subject to selection studies. For 6651 single nucleotide polymorphisms (SNPs) associated with these traits, we compared the genetic distance between Neolithic Anatolian (n=36) and presentday Anatolian (n=16) individuals, measured using the FST statistic, with SNPs in evolutionary neutral regions. Then, frequency changes of alleles that elevating phenotypes were studied, to test for a common direction of allele-frequency change affecting these traits. Finally, a population branch statistic (PBS) approach was applied to detect adaptation signals specific to the modern-day Anatolia in comparison to Neolithic Anatolia and an outgroup population. We found that the frequency of alleles related to GWAS traits broadly linked to lipid metabolism to be more differentiated between Neolithic and present-day Anatolia, than neutrally expected. Directionality analyses also suggested that such traits might have been driven by selection. Consistently, the genes showing the highest differentiation along the modern Anatolia branch in the PBS analysis were frequently associated with lipid metabolism. Our results imply that lipid metabolismrelated traits may have been subject to selective pressures in the last 10,000 years.