Intragenic compensation through the lens of deep mutational scanning.

ABSTRACT: A significant fraction of mutations in proteins are deleterious and result in adverse consequences for protein function, stability, or interaction with other molecules. Intragenic compensation is a specific case of positive epistasis when a neutral missense mutation cancels effect of a deleterious mutation in the same protein. Permissive compensatory mutations facilitate protein evolution, since without them all sequences would be extremely conserved. Understanding compensatory mechanisms is an important scientific challenge at the intersection of protein biophysics and evolution. In human genetics, intragenic compensatory interactions are important since they may result in variable penetrance of pathogenic mutations or fixation of pathogenic human alleles in orthologous proteins from rela

SUBMITTER: Azbukina N 

PROVIDER: S-EPMC9636336 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature