Emergence and propagation of epistasis in metabolic networks.

ABSTRACT: Epistasis is often used to probe functional relationships between genes, and it plays an important role in evolution. However, we lack theory to understand how functional relationships at the molecular level translate into epistasis at the level of whole-organism phenotypes, such as fitness. Here, I derive two rules for how epistasis between mutations with small effects propagates from lower- to higher-level phenotypes in a hierarchical metabolic network with first-order kinetics and how such epistasis depends on topology. Most importantly, weak epistasis at a lower level may be distorted as it propagates to higher levels. Computational analyses show that epistasis in more realistic models likely follows similar, albeit more complex, patterns. These results suggest that pairwise inter-gene

SUBMITTER: Kryazhimskiy S 

PROVIDER: S-EPMC7924954 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature