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Higher fitness yeast genotypes are less robust to deleterious mutations

Milo S. Johnson, Alena Martsul, Sergey Kryazhimskiy, Michael M. Desai
doi: https://doi.org/10.1101/675314
Milo S. Johnson
1Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138
2Quantitative Biology Initiative, Harvard University, Cambridge MA 02138
3NSF-Simons Center for Mathematical and Statistical Analysis of Biology, Harvard University, Cambridge MA 02138
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Alena Martsul
4Division of Biological Sciences, University of California San Diego, La Jolla CA 92093
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Sergey Kryazhimskiy
4Division of Biological Sciences, University of California San Diego, La Jolla CA 92093
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Michael M. Desai
1Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA 02138
2Quantitative Biology Initiative, Harvard University, Cambridge MA 02138
3NSF-Simons Center for Mathematical and Statistical Analysis of Biology, Harvard University, Cambridge MA 02138
5Department of Physics, Harvard University, Cambridge MA 02138
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  • For correspondence: mdesai@oeb.harvard.edu
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Abstract

Natural selection drives populations towards higher fitness, but second-order selection for adaptability and mutational robustness can also influence the dynamics of adaptation. In many microbial systems, diminishing returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: they have distributions of fitness effects (DFEs) with lower mean and higher variance. These shifts in the DFE arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 20, 2019.
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Higher fitness yeast genotypes are less robust to deleterious mutations
Milo S. Johnson, Alena Martsul, Sergey Kryazhimskiy, Michael M. Desai
bioRxiv 675314; doi: https://doi.org/10.1101/675314
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Higher fitness yeast genotypes are less robust to deleterious mutations
Milo S. Johnson, Alena Martsul, Sergey Kryazhimskiy, Michael M. Desai
bioRxiv 675314; doi: https://doi.org/10.1101/675314

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