Decoupling gene functions from knockout effects by evolutionary analyses.

ABSTRACT: Genic functions have long been confounded by pleiotropic mutational effects. To understand such genetic effects, we examine HAP4, a well-studied transcription factor in Saccharomyces cerevisiae that functions by forming a tetramer with HAP2, HAP3 and HAP5. Deletion of HAP4 results in highly pleiotropic gene expression responses, some of which are clustered in related cellular processes (clustered effects) while most are distributed randomly across diverse cellular processes (distributed effects). Strikingly, the distributed effects that account for much of HAP4 pleiotropy tend to be non-heritable in a population, suggesting they have few evolutionary consequences. Indeed, these effects are poorly conserved in closely related yeasts. We further show substantial overlaps of clustered

SUBMITTER: Liu L 

PROVIDER: S-EPMC8288921 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature