Human populations have faced a large number of environmental challenges during their evolutionary history and, as of today, they present a wide range of habitats and mode of subsistence. However, the extent of genetic adaptation and epigenetic responses to such environmental variation remains controversial. We first explored the power of several statistics to detect hard selective sweeps in the context of whole-genome sequencing data, and we evaluated their robustness to demography and other selection modes. Using data from the 1,000 Genomes Project and Complete Genomics, we showed that hard sweeps targeting low-frequency standing variations had played a moderate, albeit significant, role in recent human evolution. Moreover, the signals of selection detected were enriched in functional variants detected by genome-wide association studies. We then evaluated the relative impacts of genetic and environmental factors on human epigenomic diversity. To do so, we generated genome-wide genetic and DNA methylation profiles for Central African populations differing in their current habitat or in their historical lifestyle and genetic background. We found that both factors had similar critical impacts on how the global methylome is shaped, but that the biological functions affected and the mechanisms underlying DNA methylation variation strongly differed. More generally, methylation variation shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Together, this work provides new insights into the contribution of genetic adaptation and epigenetic responses to the adaptation of humans to environmental changes over different time scales.

Fundings

My PhD was funded by an ENS de Lyon PhD grant.