Negative feedback in genetic circuits confers evolutionary resilience and capacitance.

ABSTRACT: Natural selection for specific functions places limits upon the amino acid substitutions a protein can accept. Mechanisms that expand the range of tolerable amino acid substitutions include chaperones that can rescue destabilized proteins and additional stability-enhancing substitutions. Here, we present an alternative mechanism that is simple and uses a frequently encountered network motif. Computational and experimental evidence shows that the self-correcting, negative-feedback gene regulation motif increases repressor expression in response to deleterious mutations and thereby precisely restores repression of a target gene. Furthermore, this ability to rescue repressor function is observable across the Eubacteria kingdom through the greater accumulation of amino acid substitutions in ne

SUBMITTER: Marciano DC 

PROVIDER: S-EPMC4103627 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature