The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes.

ABSTRACT: The development of explanatory models of protein sequence evolution has broad implications for our understanding of cellular biology, population history, and disease etiology. Here we analyze the GTEx transcriptome resource to quantify the effect of the transcriptome on protein sequence evolution in a multi-tissue framework. We find substantial variation among the central nervous system tissues in the effect of expression variance on evolutionary rate, with highly variable genes in the cortex showing significantly greater purifying selection than highly variable genes in subcortical regions (Mann-Whitney U p = 1.4 × 10^-4). The remaining tissues cluster in observed expression correlation with evolutionary rate, enabling evolutionary analysis of genes in diverse physiologic

SUBMITTER: Evans P 

PROVIDER: S-EPMC7380284 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature