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Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust

Tzahi Gabzi, Yitzhak Pilpel, View ORCID ProfileTamar Friedlander
doi: https://doi.org/10.1101/2021.09.27.461914
Tzahi Gabzi
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel
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Yitzhak Pilpel
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel
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  • For correspondence: tamar.friedlander@mail.huji.ac.il pilpel@weizmann.ac.il
Tamar Friedlander
2The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Faculty of Agriculture, Hebrew University of Jerusalem, P.O. Box 12 Rehovot 7610001, Israel
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  • ORCID record for Tamar Friedlander
  • For correspondence: tamar.friedlander@mail.huji.ac.il pilpel@weizmann.ac.il
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Abstract

Fitness landscape mapping and the prediction of evolutionary trajectories on these landscapes are major tasks in evolutionary biology research. Evolutionary dynamics is tightly linked to the landscape topography, but this relation is not straightforward. Models predict different evolutionary outcomes depending on mutation rates: high-fitness genotypes should dominate the population under low mutation rates and lower-fitness, mutationally robust (also called ‘flat’) genotypes - at higher mutation rates. Yet, so far, flat genotypes have been demonstrated in very few cases, particularly in viruses. The quantitative conditions for their emergence were studied only in simplified single-locus, two-peak landscapes. In particular, it is unclear whether within the same genome some genes can be flat while the remaining ones are fit. Here, we analyze a previously measured fitness landscape of a yeast tRNA gene. We found that the wild type allele is sub-optimal, but is mutationally robust (‘flat’). Using computer simulations, we estimated the critical mutation rate in which transition from fit to flat allele should occur for a gene with such characteristics. We then used a scaling argument to extrapolate this critical mutation rate for a full genome, assuming the same mutation rate for all genes. Finally, we propose that while the majority of genes are still selected to be fittest, there are a few mutation hot-spots like the tRNA, for which the mutationally robust flat allele is favored by selection.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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-NC-ND 4.0 International license.
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Posted September 27, 2021.
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Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust
Tzahi Gabzi, Yitzhak Pilpel, Tamar Friedlander
bioRxiv 2021.09.27.461914; doi: https://doi.org/10.1101/2021.09.27.461914
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Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust
Tzahi Gabzi, Yitzhak Pilpel, Tamar Friedlander
bioRxiv 2021.09.27.461914; doi: https://doi.org/10.1101/2021.09.27.461914

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