Abstracts (first author)

Invited Speaker 

Epistatic constraints and evolutionary predictability on empirical fitness landscapes

Author(s): Krug J

Summary:

The adaptive dynamics of an asexual population in the space of genotypes is constrained by epistatic interactions between mutations at different genetic loci. Recent empirical studies have shown that this strongly reduces the number of mutational pathways that are accessible under conditions of strong selection and weak mutation (SSWM). In the talk I will describe statistical models for fitness landscapes that quantify evolutionary accessibility under different assumptions on the amount of epistasis as well as on the underlying genetic architecture, and show how these models can be used to classify and interpret empirical data sets. I then discuss the impact of epistatic constraints on the predictability of evolutionary trajectories in asexuals, with particular emphasis on the role of population size. With increasing population size clonal interference implies a preference for mutational steps of large effect, which leads to an increase in predictability beyond the expectation under SSWM dynamics. However, a further increase of population size reduces predictability by opening up new pathways that involve the crossing of fitness valleys by multiple mutations. This nonmonotonic pattern of evolutionary predictability is found in large-scale simulations on an empirical fitness landscape, and argued to be observable in experiments that monitor the variability of fitness trajectories among replicate populations.



Abstracts (coauthor)

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.

Exploring the evolvability of an antibiotic resistance enzyme

Author(s): DeVisser, A, Schenk M, Salverda M, Szendro I, Krug J

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.

Contacts

Chairman: Octávio S. Paulo
Tel: 00 351 217500614 direct
Tel: 00 351 217500000 ext22359
Fax: 00 351 217500028
email: mail@eseb2013.com

Address

XIV Congress of the European Society for Evolutionary Biology

Organization Team
Department of Animal Biology (DBA)
Faculty of Sciences of the University of Lisbon
P-1749-016 Lisbon
Portugal

Website

Computational Biology & Population Genomics Group 
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