Modern human alleles differentially regulate gene expression across brain regions: implications for brain evolution

Abstract

The availability of high-coverage genomes of our extinct relatives, the Neanderthals and Denisovans, and the emergence of large, tissue-specific databases of modern human genetic variation, offer the possibility of probing the evolutionary trajectory of heterogenous structures of great interest, such as the brain. Using the GTEx cis-eQTL dataset and an extended catalog of Homo sapiens-specific alleles relative to Neanderthals and Denisovans, we generated a dataset of nearly fixed, Homo sapiens-derived alleles that affect the regulation of gene expression across 15 brain (and brain related) structures. The list of variants obtained reveals enrichments in regions of the modern human genome showing putative signals of positive selection relative to archaic humans, and bring out the highly derived status of the cerebellum. Additionally, we complement previous literature on the expression effects of ancestral alleles in the Homo sapiens brain by pointing at a downregulation bias caused by linkage disequilibrium.