Unknown

Dataset Information

0

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 sef1Δ 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 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 loss-of-function triggers extensive gene expression changes responsible for compensatory, beneficial, and trade-off phenotypes. The trade-offs can be alleviated by higher cell density. Our results not only indicate that secondary transcriptional perturbation provides rapid and adaptive mechanisms potentially stabilizing the initial stage of transcriptional rewiring but also suggest how genetic polymorphisms of pleiotropic mutations could be maintained in the population.

SUBMITTER: Hsu PC 

PROVIDER: S-EPMC10240213 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Hsu Po-Chen PC   Cheng Yu-Hsuan YH   Liao Chia-Wei CW   Litan Richard Ron R RRR   Jhou Yu-Ting YT   Opoc Florica Jean Ganaden FJG   Amine Ahmed A A AAA   Leu Jun-Yi JY  

EMBO reports 20230403 6


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 sef1Δ mutant using a suppressor development strategy. Complete loss of SEF1 forces cells to initiate a compensatory process for the pl  ...[more]

Similar Datasets

| S-SCDT-10_15252-EMBR_202256019 | biostudies-other
2012-06-18 | E-GEOD-33571 | biostudies-arrayexpress
| S-EPMC2834713 | biostudies-literature
| S-EPMC10538093 | biostudies-literature
2012-06-18 | GSE33571 | GEO
| S-EPMC6393427 | biostudies-literature
| S-EPMC2764428 | biostudies-literature
| S-EPMC4758233 | biostudies-literature
| S-EPMC4856318 | biostudies-literature
| S-EPMC9344802 | biostudies-literature