Dominance vs epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles.

ABSTRACT: An important challenge in genetics, evolution and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploids, mutations in a gene can combine on the same chromosome or on different chromosomes as a "heteroallelic combination". However, a direct comparison of the extent, sign, and stability of the genetic interactions between variants within and between alleles is lacking. Here we use thermodynamic models of protein folding and ligand-binding to show that interactions between mutations within and between alleles are expected in even very simple biophysical systems. Protein folding alone generates within-allele interactions and a single molecular interaction is sufficient to cause between-allele inter

SUBMITTER: Xie X 

PROVIDER: S-EPMC10492795 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature