Our research interests

We are evolutionary geneticists, interested in questions of how the interactions among genes evolve, and how those interactions in turn affect processes of evolution. Our work has both empirical and theoretical components, and one of our constant goals is to integrate the two as much as possible, so that theoretical results generate predictions for experiments, while experimental results help focus future theoretical work.

We have three main areas of research, outlined below, all of which relate to several very general questions in evolutionary biology, in particular:

• How does an individual's genotype map onto its fitness?
• To what extent does the environment, both biotic and abiotic, affect the fitness of some genotypes relative to others?
• How do the molecular details of genomic processes affect the evolution of those processes?

The evolution of recombination rates in laboratory populations of the roundworm Caenorhabditis elegans

Because the effective recombination rate of C. elegans can be manipulated at several levels, we are able to test evolutionary models of recombination by exposing populations with different recombination rates to environmental or genetic perturbations that would be predicted to provide an advantage to recombination. For example, one broad class of models predicts that populations with high recombination rates should adapt more quickly to novel environments. If fitness increases more rapidly in high-recombination populations of C. elegans than in low-recombination populations when both are subjected to the same new environment, then this class of models is supported. Molecular approaches for determining what loci are involved in adaptation can then be applied to help determine what specific processes are involved in providing an advantage to recombination.

The evolution of fitness via compensatory mutations in C. elegans

If a genotype has had its fitness reduced due to mutations, is it more likely to encounter mutations at other loci that increase its fitness? In other words, can mutations, which might otherwise be neutral or deleterious, increase fitness by compensating for the disadvantageous effects of mutations at other loci? How common are such "compensatory mutations;" what are their effects; and to what extent do their effects depend on the genetic specifics of the original fitness-reducing mutations? The answer to this question has implications for our understanding of the degree to which genomes are integrated, which in turn informs our understanding of processes like speciation and the evolution of sex. In addition, this question has implications for species conservation, since endangered populations are expected to accumulate fitness-reducing mutations; if such populations have a high rate of compensatory mutation, they may be more likely to survive than we originally thought. We address such questions by allowing strains of C. elegans that are "knockouts" at arbitrarily chosen loci (i.e., they've had stretches of protein-coding DNA excised completely) to evolve. Any increases in fitness are then due to compensatory mutations at other loci. Using a combination of statistical and genetic approaches, we can estimate the numbers and effects of compensatory mutations across large numbers of lines.

Theoretical models of the evolution of sex and recombination

We use computer simulation as well as numerical and analytical approaches to achieve two ends: (1) to generate experimentally useful predictions from the wide array of models currently available to explain sex and recombination; and (2) to integrate these models into a common, modern model framework -- a stochastic framework explicitly considering the probability of fixation of alleles that affect the rate of sex or recombination.

Our primary theoretical focus of late is on the evolution of recombination hotspots, which pose a long-standing paradox in evolutionary genetics. Most crossover events in many eukaryotes appear to occur at relatively small locations in the genome -- "recombination hotspots." If these hotspots are defined by the DNA sequence at the hotspots themselves, they are expected to recombine themselves out of existence, since recombination appears to be initiated by the conversion of the sequence on one chromatid by sequence on the homologous chromatid. If, as appears to be the case, hot alleles are preferentially converted by their cold homologues in heterozygotes, hotspots should "drive" themselves out of existence. We are exploring ways around this paradox, particularly through the combination of hotspot control by the sequence at the hotspot itself and by sequence elsewhere in the genome. We are also interested in exploring to what extent this discrete, hotspot-controlled mechanism of recombination constrains the evolution of broader scale recombination rates.