Understanding the Evolutionary Fate of Finite Populations: The Dynamics of Mutational Effects

Abstract

The most consistent result in more than two decades of experimental evolution is that the fitness of populations adapting to a constant environment does not increase indefinitely, but reaches a plateau. Using experimental evolution with bacteriophage, we show here that the converse is also true. In populations small enough such that drift overwhelms selection and causes fitness to decrease, fitness declines down to a plateau. We demonstrate theoretically that both of these phenomena must be due either to changes in the ratio of beneficial to deleterious mutations, the size of mutational effects, or both. We use mutation accumulation experiments and molecular data from experimental evolution to show that the most significant change in mutational effects is a drastic increase in the rate of beneficial mutation as fitness decreases. In contrast, the size of mutational effects changes little even as organismal fitness changes over several orders of magnitude. These findings have significant implications for the dynamics of adaptation. In any population, two factors determine whether the average fitness of individuals will increase (adaptation) or decrease: the size of the population and the distribution of mutational effects (i.e., the relative rates and effect sizes of beneficial and deleterious mutations). Although it is relatively simple to get quantitative information on population size, it is much harder to gain insight into the distribution of mutational effects. Very little information exists on the relative rates of beneficial versus deleterious effects, on the shapes of mutational distributions, or on whether the distributions change over time. Thus, it remains difficult to even speculate whether a given population will adapt over time. Here, we use laboratory evolution of a bacterial virus to quantify the distribution of mutational effects. Our results reveal that the average impact of a mutation is approximately constant with respect to fitness, that most mutations have small effects, and that the rate of beneficial mutation depends on the fitness of the organism. Our study demonstrates the simple, but perhaps underappreciated fact that mutational effects are dynamic. It also proposes and tests an explicit model of adaptation in which organismal fitness specifies both the rate and distribution of deleterious and beneficial mutations, and it presents specific and testable predictions of the circumstances under which populations will adapt.