The last Department Seminar of the year will be given by Claudia Bank from the Instituto Gulbenkian de Ciencia, at 14:00 in D502.

One (small) step at a time: the distribution of fitness effects of yeast mutations under different stresses

Recent technological advances have made it possible to experimentally screen the fitness effects of thousands of engineered mutations simultaneously, which carries the promise to answer fundamental evolutionary questions regarding the potential for adaptation, the ubiquitousness of purifying selection, and the presence of epistasis. Here we systematically measured fitness effects of all 14598 single-step amino-acid changing mutations along the complete sequence of the heat-shock protein Hsp90 in yeast. Across all environments, we observed that the fitness of a large percentage (up to 80%) of mutations is indistinguishable from that of the reference genotype. Consistent with classical models of adaptation, we found the largest numbers of deleterious and beneficial mutations in the most stressful environments. By estimating the sensitivity of the distribution of fitness effects (DFE) to environmental changes at each amino-acid position, we found that the change of fitness effects is largely due to shifts in the mean DFE rather than shuffling of mutational effects. Thus, so-called "costs of adaptation" that appear when mutational effects change their sign across environments are rare. Our results support the hypothesis that structural properties of the mutated amino acid position are the dominant constraint on new mutations across all environments. We also compare our DFEs with expectations obtained from natural sequence data and discuss how these results support classical population genetic theories.

Rhonda Snook & Rike Stelkens