PT  - JOURNAL ARTICLE
AU  - Tzahi Gabzi
AU  - Yitzhak Pilpel
AU  - Tamar Friedlander
TI  - Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust
AID  - 10.1101/2021.09.27.461914
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.27.461914
4099  - http://biorxiv.org/content/early/2021/09/27/2021.09.27.461914.short
4100  - http://biorxiv.org/content/early/2021/09/27/2021.09.27.461914.full
AB  - 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 StatementThe authors have declared no competing interest.