Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis

Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins enhancing the evolvability, has therefore attracted interest. However, our current understand...

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Autores principales: Persson, Karl, Stenberg, Simon, Tamás, Markus J, Warringer, Jonas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635671/
https://www.ncbi.nlm.nih.gov/pubmed/36083011
http://dx.doi.org/10.1093/g3journal/jkac240
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author Persson, Karl
Stenberg, Simon
Tamás, Markus J
Warringer, Jonas
author_facet Persson, Karl
Stenberg, Simon
Tamás, Markus J
Warringer, Jonas
author_sort Persson, Karl
collection PubMed
description Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins enhancing the evolvability, has therefore attracted interest. However, our current understanding of how genes influence adaptation kinetics is limited, partly because accurately measuring adaptation for many cell populations is challenging. We used a high-throughput adaptive laboratory evolution platform to track the adaptation of >18,000 cell populations corresponding to single-gene deletion strains in the haploid yeast deletion collection. We report that the preadaptation fitness of gene knockouts near-perfectly (R(2)= 0.91) predicts their adaptation to arsenic, leaving at the most a marginal role for dedicated evolvability gene functions. We tracked the adaptation of another >23,000 gene knockout populations to a diverse range of selection pressures and generalized the almost perfect (R(2)=0.72–0.98) capacity of preadaptation fitness to predict adaptation. We also reconstructed mutations in FPS1, ASK10, and ARR3, which together account for almost all arsenic adaptation in wild-type cells, in gene deletions covering a broad fitness range and show that the predictability of arsenic adaptation can be understood as a by global epistasis, where excluding arsenic is more beneficial to arsenic unfit cells. The paucity of genes with a meaningful evolvability effect on adaptation diminishes the prospects of developing adjuvant drugs aiming to slow antimicrobial and chemotherapy resistance.
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spelling pubmed-96356712022-11-07 Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis Persson, Karl Stenberg, Simon Tamás, Markus J Warringer, Jonas G3 (Bethesda) Mutant Screen Report Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins enhancing the evolvability, has therefore attracted interest. However, our current understanding of how genes influence adaptation kinetics is limited, partly because accurately measuring adaptation for many cell populations is challenging. We used a high-throughput adaptive laboratory evolution platform to track the adaptation of >18,000 cell populations corresponding to single-gene deletion strains in the haploid yeast deletion collection. We report that the preadaptation fitness of gene knockouts near-perfectly (R(2)= 0.91) predicts their adaptation to arsenic, leaving at the most a marginal role for dedicated evolvability gene functions. We tracked the adaptation of another >23,000 gene knockout populations to a diverse range of selection pressures and generalized the almost perfect (R(2)=0.72–0.98) capacity of preadaptation fitness to predict adaptation. We also reconstructed mutations in FPS1, ASK10, and ARR3, which together account for almost all arsenic adaptation in wild-type cells, in gene deletions covering a broad fitness range and show that the predictability of arsenic adaptation can be understood as a by global epistasis, where excluding arsenic is more beneficial to arsenic unfit cells. The paucity of genes with a meaningful evolvability effect on adaptation diminishes the prospects of developing adjuvant drugs aiming to slow antimicrobial and chemotherapy resistance. Oxford University Press 2022-09-09 /pmc/articles/PMC9635671/ /pubmed/36083011 http://dx.doi.org/10.1093/g3journal/jkac240 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Mutant Screen Report
Persson, Karl
Stenberg, Simon
Tamás, Markus J
Warringer, Jonas
Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title_full Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title_fullStr Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title_full_unstemmed Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title_short Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
title_sort adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis
topic Mutant Screen Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635671/
https://www.ncbi.nlm.nih.gov/pubmed/36083011
http://dx.doi.org/10.1093/g3journal/jkac240
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