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- Persson, Karl,1988Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg (author)
Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis.
- Article/chapterEnglish2022
Publisher, publication year, extent ...
- 2022-09-09
- Oxford University Press (OUP),2022
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- LIBRIS-ID:oai:gup.ub.gu.se/321007
- https://gup.ub.gu.se/publication/321007URI
- https://doi.org/10.1093/g3journal/jkac240DOI
- https://research.chalmers.se/publication/532650URI
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- Language:English
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- 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 (R2= 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 (R2=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.
Subject headings and genre
- NATURVETENSKAP Biologi Evolutionsbiologi hsv//swe
- NATURAL SCIENCES Biological Sciences Evolutionary Biology hsv//eng
- NATURVETENSKAP Biologi Genetik hsv//swe
- NATURAL SCIENCES Biological Sciences Genetics hsv//eng
- NATURVETENSKAP Biologi Mikrobiologi hsv//swe
- NATURAL SCIENCES Biological Sciences Microbiology hsv//eng
- MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
- Saccharomyces cerevisiae
- genetics
- metabolism
- Epistasis
- Genetic
- Genetic Fitness
- Gene Knockout Techniques
- Arsenic
- metabolism
- Adaptation
- Physiological
- genetics
- Mutation
- Evolution
- Molecular
- epistasis
Added entries (persons, corporate bodies, meetings, titles ...)
- Stenberg, SimonGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,University of Gothenburg (author)
- Tamás, Markus J.,1970Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,University of Gothenburg(Swepub:gu)xtamma (author)
- Warringer, Jonas,1973Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,University of Gothenburg(Swepub:gu)xwarrj (author)
- Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)
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- In:G3 (Bethesda, Md.): Oxford University Press (OUP)12:112160-1836
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