Derived Homo sapiens cis-eQTL regulation: implications for brain evolution

Derived Homo sapiens cis-eQTL regulation: implications for brain evolution

Abstract

The high-quality sequence of the genomes of our extinct relatives, Neanderthals and Denisovans, became recently public. At the same time, we have seen the emergence of big databases of modern human genetic variation. However, linking human genetic variation, neuronal phenotypes and, eventually, behaviour, is only possible if we understand how variation and genetic regulation interact. We used two publicly available datasets, the GTEX cis-eQTL database (v7) and a catalog of high-frequency Homo sapiens specific alleles relative to the Neanderthals and Denisovan sequences, to understand how high-frequency Homo Sapiens derived alleles affect gene expression regulation. The resulting dataset shows that genes associated with brain development are affected by Homo sapiens-specific eQTL in brain areas key in human evolution such as the cerebellum. We also show that some of these eQTL overlap significantly with putative regions of positive selection relative to archaic humans (Peyregne et al., 2017). Additionally, we tested whether any of the variants are associated with clinical conditions in modern human populations. These findings can inform future experimental work and enrich current venues of research of the Homo Sapiens brain evolution, such as the relationship between clinical and evolutionary research and the recent expansion of the cerebellum in Homo Sapiens (Gunz et al., 2010)

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