Dynamics of molecular evolution in RNA virus populations depend on sudden versus gradual environmental change

Abstract

Understanding the dynamics of molecular adaptation is a fundamental goal of evolutionary biology. While adaptation to constant environments has been well characterized, the effects of environmental complexity remain seldom studied. One simple but understudied factor is the rate of environmental change. Here we used experimental evolution with RNA viruses to investigate whether evolutionary dynamics varied based on the rate of environmental turnover. We used whole-genome next-generation sequencing to characterize evolutionary dynamics in virus populations adapting to a sudden versus gradual shift onto a novel host cell type. In support of theoretical models, we found that when populations evolved in response to a sudden environmental change, mutations of large beneficial effect tended to fix early, followed by mutations of smaller beneficial effect; as predicted, this pattern broke down in response to a gradual environmental change. Early mutational steps were highly parallel across replicate populations in both treatments. The fixation of single mutations was less common than sweeps of associated "cohorts" of mutations, and this pattern intensified when the environment changed gradually. Additionally, clonal interference appeared stronger in response to a gradual change. Our results suggest that the rate of environmental change is an important determinant of evolutionary dynamics in asexual populations.

Keywords: Adaptation; Sindbis virus; clonal interference; epistasis; experimental evolution.

Figure 1

Trajectory plots showing the frequency of mutations relative to the ancestral sequence over time. Each plot shows dynamics in a single virus population over the course of the experiment (nine populations per treatment). Each line tracks the frequency of one mutation at each passage. Colors indicate the gene in which the mutation occurs or mark the mutation as being in an untranslated region. (A) SINV populations evolved in sudden host‐change treatment. (B) SINV populations evolved in gradual host‐change treatment.

Figure 2

Distribution and correlation with fixation times for S_up values. (A) Histograms showing the distribution of S_up values for the total set of mutations for which S_up was calculated and for those in each treatment. (B) Mutational S_up values versus the passage at which that mutation reaches fixation or majority. Upper panels (blue) show relationships for sudden treatment, lower panels (pink) show relationships for gradual treatment.

Figure 3

Analysis of mutational cohorts. (A) Counts of mutations classified as singletons and mutations classified as members of cohorts for each virus population. Each point represents the number of singletons or mutations in cohorts for a single virus population. Means and 95% CI are shown in red. (B) The distribution of cohort sizes by treatment. Here, singletons are considered cohorts of one.

Figure 4

Likelihood of mutational loss. (A) Likelihood of loss H(x) after reaching frequency x for nonsynonymous and synonymous mutations. (B) A summary ratio h(x) calculated over the whole dataset. When h(x) > 1 (threshold marked by line), nonsynonymous mutations are lost at a higher rate than synonymous mutations.