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Updated: Jun 7, 2025

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Progressive transcriptomic shifts in evolved yeast strains following gene knockout.

Bei Jiang1,2, Chuyao Xiao1,3,4, Li Liu1

  • 1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

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Gene knockout in yeast strains disrupts cellular homeostasis. Adaptive evolution experiments show cells struggle to regain their original gene expression state, instead adopting distinct suboptimal compensatory states.

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Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Systems Biology

Background:

  • Gene knockout perturbs cellular homeostasis, leading to altered gene expression and phenotypes.
  • Understanding the long-term transcriptomic consequences of genetic perturbations is crucial for cellular biology.

Purpose of the Study:

  • To investigate the adaptive evolution of yeast strains following gene knockout (hap4Δ and ade1Δ).
  • To determine if cells can return to their pre-knockout transcriptomic state after genetic disruption.

Main Methods:

  • Adaptive evolution experiments were conducted on hap4Δ and ade1Δ yeast strains.
  • Transcriptomic analysis was performed to compare gene expression profiles of knockout and evolved strains to the wild-type.

Main Results:

  • Genes with higher wild-type expression and more interaction partners were initially more likely to be restored.
  • Most initially restored genes became unrestored as evolution progressed; over 60% of differentially expressed genes remained unrestored.
  • Evolved strains developed distinct transcriptomic states, diverging from the original strain, with systematic changes in ribosome biogenesis components.

Conclusions:

  • Yeast knockout strains exhibit significant difficulty in returning to their original transcriptomic state, even after extended culture.
  • Compensatory mechanisms drive evolved strains into distinct, suboptimal transcriptomic states, illustrating complex post-perturbation dynamics.