Antagonistic pleiotropy conceals molecular adaptations in changing environments

The importance of positive selection in molecular evolution is debated. Evolution experiments under invariant laboratory conditions typically show a higher rate of nonsynonymous nucleotide change than that of synonymous change, demonstrating prevalent molecular adaptations. Natural evolution inferred from genomic comparisons, however, almost always exhibits the opposite pattern even among closely related conspecifics, indicative of a paucity of positive selection. We hypothesize that this apparent contradiction is at least in part attributable to ubiquitous and frequent environmental changes in nature, causing nonsynonymous mutations beneficial at one time deleterious soon after because of antagonistic pleiotropy and hindering their fixations relative to synonymous mutations despite continued population adaptations. Indeed, our yeast evolution experiments in changing and corresponding constant environments support this hypothesis, suggesting that molecular adaptation is consistently underestimated in nature due to the antagonistic fitness effects of mutations in changing environments.