Rapid evolutionary repair by secondary perturbation of a primary disrupted transcriptional network

ABSTRACT: The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection. A conflict-free switch of a regulon between regulators may require an immediate compensatory evolution to minimize deleterious effects. Here, we perform an evolutionary repair experiment on the Lachancea kluyveri yeast sef1 mutant using a suppressor development strategy. Complete loss of SEF1 forces cells to initiate a compensatory process for the pleiotropic defects arising from misexpression of TCA cycle genes. Using different selective conditions, we respectively identify two adaptive loss-of-function mutations of IRA1 and AZF1. Subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 los

SUBMITTER: Dr. Po-Chen Hsu 

PROVIDER: S-SCDT-10_15252-EMBR_202256019 | biostudies-other |

REPOSITORIES: biostudies-other