The trait specific timing of accelerated genomic change in the human lineage

Abstract

Humans exhibit distinct characteristics compared to our primate and ancient hominin ancestors including bipedal locomotion and enhanced neurocognitive ability, but the timing of accelerated changes in these traits is uncertain. To investigate if specific trait-associated variation show enrichment during particular periods of human evolution, we combine genome wide association study (GWAS) data from 70 traits, spanning multiple categories including AI-based image-derived morphological phenotypes of the brain, heart, and skeletal tissues with data from 12 different evolutionary regions obtained from comparative functional genomics, multi-species alignments from long read sequencing, and ancient DNA reflecting 4 different major evolutionary divergence points. These regions cover epigenetic differences in the brain between humans and rhesus macaques, various human accelerated regions (HARs) including regions from the Zoonomia Project, ancient selective sweeps, and Neanderthal introgressed alleles. Using two complementary approaches to examine enrichment between GWAS loci and genomic regions, we show that more phenotypes are enriched in earlier periods of divergence of humans with macaques and chimps, and less so during the divergence with Neanderthals. These traits span respiratory, dermatological, reproductive, metabolic, and psychiatric domains along with skeletal and brain imaging traits, consistent with striking morphological changes between humans and other primates. Among brain imaging traits, we observe an enrichment of SNPs associated with the longitudinal fasciculus in human-gained epigenetic elements since macaques, the visual cortex in HARs, and the thalamus proper in Neanderthal introgressed alleles, implying associated functions such as language processing, decision making, relay of sensory signals, and motor control are enriched at different evolutionary depths.