Person:

Frenkel, Evgeni

The outcomes of evolution are determined by which mutations occur and fix. In rapidly adapting microbial populations, this process is particularly hard to predict because lineages with different beneficial mutations often spread simultaneously and interfere with one another’s fixation. Hence to predict the fate of any individual variant, we must know the rate at which new mutations create competing lineages of higher fitness. Here, we directly measured the effect of this interference on the fates of specific adaptive variants in laboratory Saccharomyces cerevisiae populations and used these measurements to infer the distribution of fitness effects of new beneficial mutations. To do so, we seeded marked lineages with different fitness advantages into replicate populations and tracked their subsequent frequencies for hundreds of generations. Our results illustrate the transition between strongly advantageous lineages that decisively sweep to fixation and more moderately advantageous lineages that are often outcompeted by new mutations arising during the course of the experiment. We developed an approximate likelihood framework to compare our data to simulations and found that the effects of these competing beneficial mutations were best approximated by an exponential distribution, rather than one with a single effect size. We then used this inferred distribution of fitness effects to predict the rate of adaptation in a set of independent control populations. Finally, we discuss how our experimental design can serve as a screen for rare, large-effect beneficial mutations.

Natural selection gives rise to biodiversity by purging the less-fit among variants that are too similar (a principle known as character displacement), but to predict how fit or different an organism needs to be to survive is hard. In the simplest theoretical case, the probability whether one lineage versus another survives depends only on their relative fitness and random fluctuations. In more complex scenarios, this probability may depend on the fitness of all the other lineages in the population, mutations that these and other lineages acquire before the outcome of competition is decided, and additional ecological interactions. These complexities evolve readily in laboratory microbial populations, suggesting that they are the norm in Nature, and have been extensively studied theoretically. This thesis provides one of the few empirical examples in which the evolution and mechanism of some of these complexities have been characterized and modeled sufficiently to make basic predictions, such as whether a mutation will fix or go extinct, which competing lineages may or may not coexist, and how do these processes relate? This work was carried out in an established system for experimental evolution, populations of asexual budding yeast (S. cerevisiae) in microtiter plates.

Chapter 2 demonstrates an experimental design and modeling approach to infer the distribution of fitness effects of beneficial mutations from the population-dynamics of genetic markers. The inferred distribution accurately predicts fixation probabilities of lineages and adaptation rates of populations. Chapter 3 describes a new example of spontaneously-evolved coexistence between types competing for the same resources, including the physical mechanism, genetic basis and a mathematical model of the coexistence. The conclusion provides additional analyses to connect the findings from these two chapters and discusses their implications for microbial evolution more generally and directions for future work.

Identifying the mechanisms that create and maintain biodiversity is a central challenge in biology. Stable diversification of microbial populations often requires the evolution of differences in resource utilization. Alternatively, coexistence can be maintained by specialization to exploit spatial heterogeneity in the environment. Here, we report spontaneous diversification maintained by a related but distinct mechanism: crowding avoidance. During experimental evolution of laboratory Saccharomyces cerevisiae populations, we observed the repeated appearance of “adherent” (A) lineages able to grow as a dispersed film, in contrast to their crowded “bottom-dweller” (B) ancestors. These two types stably coexist because dispersal reduces interference competition for nutrients among kin, at the cost of a slower maximum growth rate. This tradeoff causes the frequencies of the two types to oscillate around equilibrium over the course of repeated cycles of growth, crowding, and dispersal. However, further coevolution of the A and B types can perturb and eventually destroy their coexistence over longer time scales. We introduce a simple mathematical model of this “semistable” coexistence, which explains the interplay between ecological and evolutionary dynamics. Because crowded growth generally limits nutrient access in biofilms, the mechanism we report here may be broadly important in maintaining diversity in these natural environments.