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Professor Fernando Villanea's co-authored article published in GBE (Genome Biology and Evolution).Ìý This article is a collaboration between his lab and Dr. Katrina Claw, who is an anthropologistÌýat the School of Medical Sciences at CU Anschutz.

Abstract

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes—genes responsible for the processing of exogenous substances such as food, pollutants, and medications—as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11ÌýCYP450Ìýgenes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaicÌýCYP450Ìýgenes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaicÌýCYP450Ìýgenes that are novel and unique to archaic humans as well as one gene,ÌýCYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlightÌýCYP2A6,ÌýCYP2C9, andÌýCYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.

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