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. Here we cross two publicly available datasets, the GTEX cis-eQTL database (version 8) and an extended catalog of Homo sapiens specific alleles relative to the Neanderthal and Denisovan sequences to understand how nearly fixed Sapiens-derived alleles affect the regulation of gene expression across 15 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, points to associations with clinical conditions, and places the focus on specific structures such as the cerebellum and the Hypothalamus-Pituitary-Adrenal Gland axis. The directionality of regulation of these variants complements earlier findings about introgressed variants from archaics, and highlights the role of genes that deserve closer experimental attention.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Data source updated from GTEx version 7 to 8; reproducibility with the inclusion of the code used to generate the data and figures; rewriting of most of the text to reflect new results with updated dataset version, and to clarify.