Most models describing the evolution of recombination have focused on the case of a single population, implicitly assuming that all individuals are equally likely to mate and that spatial heterogeneity in selection is absent. In these models, the evolution of recombination is driven by linkage disequilibria generated either by epistatic selection or drift. Models based on epistatic selection sh...

The prevalence of sexual reproduction remains one of the most perplexing phenomena in evolutionary biology. The deterministic mutation hypothesis postulates that sexual reproduction will be advantageous under synergistic epistasis, a condition in which mutations cause a greater reduction in fitness when combined than would be expected from their individual effects. The inverse condition, antago...

In this paper, we examine the conditions that allow increased recombination to evolve in the presence of recurrent deleterious mutation. We focus on a three-locus model first studied by Feldman et al. (1980), which follows the dynamics of a modifier locus that alters the recombination rate between two loci subject to deleterious mutation. Although Feldman et al. (1980) indicated that increased ...

Gene expression data has been used in lieu of phenotype in both classical and quantitative genetic settings. These two disciplines have separate approaches to measuring and interpreting epistasis, which is the interaction between alleles at different loci. We propose a framework for estimating and interpreting epistasis from a classical experiment that combines the strengths of each approach. A...

We revisit the model by Wiser, Ribeck, and Lenski (Science 342 (2013), 1364–1367), which describes how the mean fitness increases over time due to beneficial mutations in Lenski’s long-term evolution experiment. We develop the model further both conceptually and mathematically. Conceptually, we describe the experiment with the help of a Cannings model with mutation and selection, where the latt...

Mapping protein sequence space is a difficult problem that necessitates the analysis of 20(N) combinations for sequences of length N. We systematically mapped the sequence space of four key residues in the Escherichia coli protein kinase PhoQ that drive recognition of its substrate PhoP. We generated a library containing all 160,000 variants of PhoQ at these positions and used a two-step select...

Many birth defects and genetic diseases are expressed in individuals that do not carry the disease causing alleles. Genetic diseases observed in offspring can be caused by gene expression in mothers and by interactions between gene expression in mothers and offspring. It is not clear whether the underlying pattern of gene expression (maternal versus offspring) affects the incidence of genetic d...

We study the evolution of robustness in digital organisms adapting to a high mutation rate. As genomes adjust to the harsh mutational environment, the mean effect of single mutations decreases, up until the point where a sizable fraction (up to 30% in many cases) of the mutations are neutral. We correlate the changes in robustness along the line of descent to changes in directional epistasis, a...

In this note we measure the interdependency of bits in the encoding of a fitness function using two different invariants. The first invariant, normalized epistasis, features a strong correlation with GA-hardness, as we illustrate here with generalized Royal Road functions. The second one, bit decidability, imitates epistasis, but has the avantage of being less difficult to calculate and approxi...

Xiang Zhang: Efficient Algorithms for Detecting Genetic Interactions in Genome-Wide Association Study. (Under the direction of Wei Wang.) Genome-wide association study (GWAS) aims to find genetic factors underlying complex phenotypic traits, for which epistasis or gene-gene interaction detection is often preferred over a single-locus approach. However, the computational burden has been a major ...