Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

Historical contingency and diminishing returns epistasis have been typically studied for relatively divergent genotypes and/or over long evolutionary timescales. Here, we use Saccharomyces cerevisiae to study the extent of diminishing returns and the changes in the adaptive mutational spectra following a single first adaptive mutational step. We further evolve three clones that arose under identical conditions from a common ancestor. We follow their evolutionary dynamics by lineage tracking and determine adaptive outcomes using fitness assays and whole genome sequencing. We find that diminishing returns manifests as smaller fitness gains during the 2(nd) step of adaptation compared to the 1(st) step, mainly due to a compressed distribution of fitness effects. We also find that the beneficial mutational spectra for the 2(nd) adaptive step are contingent on the 1(st) step, as we see both shared and diverging adaptive strategies. Finally, we find that adaptive loss-of-function mutations, such as nonsense and frameshift mutations, are less common in the second step of adaptation than in the first step. Analyses of both natural and experimental evolution suggest that adaptation depends on the evolutionary past and adaptive potential decreases over time. Here, by tracking yeast adaptation with DNA barcoding, the authors show that such evolutionary phenomena can be observed even after a single adaptive step.

Automated summary

Diminishing returns are observed in the fitness gains during the second step of adaptation compared to the first step, due to a compressed distribution of fitness effects. The beneficial mutational spectra for the second adaptive step are contingent on the first step, with both shared and diverging adaptive strategies. Loss-of-function mutations are less common in the second step of adaptation, suggesting that adaptive potential decreases over time.