Summary:

The adaptation of large asexual populations is hampered by the competition between independently arising beneficial mutations in different individuals, which is known as clonal interference. In classic work, Fisher and Muller proposed that recombination provides an evolutionary advantage in large populations by alleviating this competition. Based on recent progress in quantifying the speed of adaptation in asexual populations undergoing clonal interference, we present a detailed analysis of the Fisher-Muller mechanism for a model genome consisting of two loci with an infinite number of beneficial alleles each and multiplicative (non-epistatic) fitness effects. We solve the deterministic, infinite population dynamics exactly and show that, for a particular, natural mutation scheme, the speed of adaptation in sexuals is twice as large as in asexuals. This result is argued to hold for any nonzero value of the rate of recombination. Guided by the infinite population result and by previous work on asexual adaptation, we postulate an expression for the speed of adaptation in finite sexual populations that agrees with numerical simulations over a wide range of population sizes and recombination rates. The ratio of the sexual to asexual adaptation speed is a function of population size that increases in the clonal interference regime and approaches 2 for extremely large populations. The simulations also show that recombination leads to a strong equalization of the number of fixed mutations in the two loci. The generalization of the model to an arbitrary number $L$ of loci is briefly discussed. For a particular communal recombination scheme, the ratio of the sexual to asexual adaptation speed is approximately equal to $L$ in large populations.

Summary:

For a quantitative understanding of the process of adaptation, we need to understand its ‘raw material’, that is the properties of beneficial mutations. In my talk, I will focus on two properties in particular, the frequency distribution of fitness effects of beneficial mutations and their epistatic interactions, and how these determine the pathway and outcome of evolution. In the experiments that I will present, we study the in vitro evolution of the enzyme TEM-1 beta-lactamase, a notorious determinant of antibiotic resistance in bacteria. The first two studies are systematic investigations of the short-term evolvability of the enzyme, including the number and effects of beneficial mutations and their epistatic interactions. The last two studies address the role of the structure of the fitness landscape (caused by epistasis) and population size on long-term evolvability. Surprisingly, we find that small populations sometimes reach higher resistance than large populations, showing the important role of chance events for long-term adaptation.