Protein dynamics provide mechanistic insights about epistasis among common missense polymorphisms.

ABSTRACT: Sequencing of the protein coding genome has revealed many different missense mutations of human proteins and different population frequencies of corresponding haplotypes, which consist of different sets of those mutations. Here, we present evidence for pairwise intramolecular epistasis (i.e., nonadditive interactions) between many such mutations through an analysis of protein dynamics. We suggest that functional compensation for conserving protein dynamics is a likely evolutionary mechanism that maintains high-frequency mutations that are individually nonneutral but epistatically compensating within proteins. This analysis is the first of its type to look at human proteins with specific high population frequency mutations and examine the relationship between mutations that make up that obs

SUBMITTER: Ose NJ 

PROVIDER: S-EPMC10398253 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature