Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations

Abstract

The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance, the response of pathogens to immune selection, and the dynamics of cancer progression. In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly, but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational 'cohorts'. Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favours parallel evolutionary solutions in replicate populations.

Figure 1. The fates of individual spontaneously arising mutations

We show the frequency of all identified mutations through 1,000 generations in 6 of the 40 sequenced populations. Nonsynonymous mutations are solid lines with solid circles, while synonymous and intergenic mutations are dotted lines with open circles and squares respectively. Populations in the left and right columns were evolved at small (10⁵) and large (10⁶) population sizes, respectively. We observe qualitatively similar patterns in the other populations (Supplementary Fig. 1).

Figure 2. Statistical analysis across 40 replicate populations

a, The per-population number of total mutations, fixed mutations, extinct mutations, and mutations that are currently polymorphic over the course of the 1,000 generations. b, The distribution of the number of new mutations detected at each timepoint (solid blue line; see Methods for details) and a Poisson distribution with the same mean (dashed red line). c–d, Mutation fixation probability as a function of initial relative fitness. Data are mean±s.e.m.

Figure 3. The dynamics of sequence evolution in BYB1-G07

a, The trajectories of the 15 mutations that attain a frequency of at least 30%, hierarchically clustered into several distinct mutation “cohorts,” each of which is represented by a different color (Methods). b, Muller diagram showing the dynamics of the six main cohorts in the population. The number of times a mutation was observed in a given gene across all 40 populations is indicated in parentheses. Mutations in genes observed in more than three replicate populations (Table 1) are indicated in bold.

Figure 4. Genetic dissection of BYS1-A08

a, The trajectories of observed mutations. b, We crossed evolved clones from generation 545 to the ancestor; shown here are the fitnesses and genotypes of parental clones and 80 haploid progeny.