Loss-of-function mutations are main drivers of adaptations during short-term evolution

Abstract

We noticed that during short-term experimental evolution and carcinogenesis, mutations causing gene inactivation (i.e., nonsense mutations or frameshifts) are frequent. Our meta-analysis of 65 experiments using modified dN/dS statistics indicated that nonsense mutations are adaptive in different experimental conditions and we empirically confirmed this prediction. Using yeast S. cerevisiae as a model we show that fixed or highly frequent gene loss-of-function mutations are almost exclusively adaptive in the majority of experiments.

Figure 1

The estimations of fraction of beneficial nonsense mutations in various studies.

Figure 2

Competition of wild-type and mutant S. cerevisiae strains under various culturing conditions. Competition assays were performed for hog1Δ, pbs2Δ, rim15Δ, ure2Δ, whi2Δ, and wild-type S. cerevisiae W303 strains. The cell ratio of the mutant and wild-type strains was monitored by plating ca. 100 cells onto the YPD solid medium and replicating grown colonies onto the same medium supplemented with geneticin to distinguish the mutant cells from the wild-type cells. Data for each graph represents the mean ∓ SD of at least three independent assays.

Figure 3

Flow chart showing articles and data selection process.