Evolutionary population genetics
The ability to obtain complete genome sequences of complex eukaryotic organisms at moderate cost has revolutionized evolutionary genetics and has opened up fundamental questions that were previously beyond reach. We have sequenced the genomes of samples of wild house mice and brown rats from their ancestral ranges in NW India and China, respectively, and are using these to address several questions concerning the interactions between natural selection, new mutations, finite population size and genetic linkage in the mammalian genome. Studying wild house mice is advantageous, because their effective population sizes are extremely large (nearly two orders of magnitude larger than humans, for example), so signatures of natural selection in the genome are considerably easier to detect and accurately quantify. In contrast, we have found that wild brown rats have a much smaller effective population size than wild mice. We are particularly interested in quantifying the relative contributions of mutations in coding versus regulatory DNA to evolutionary adaptation and in understanding the causes of variation in nucleotide diversity across the genome. This work was previously funded by the Wellcome Trust and is now founded by the European Research Council (ERC).
The nature of spontaneous variation from new mutations
The genetic variation we see within populations and between different populations, including different species, originates from spontaneous mutations. An improved understanding of genetic variation and the genetic basis of evolutionary change can therefore be achieved by a better understanding of the nature of new variation from spontaneous mutations. The ERC has funded us to carry out a long term spontaneous mutation accumulation (MA) experiment in laboratory mice. We are maintaining multiple inbred sublines derived from several different inbred strains for a period of several years. We will quantify the rate of change in the mean and variance for quantitative traits, including major components of fitness along with growth and skeletal traits. We will also track the accumulation of inherited molecular changes by whole-genome sequencing. This work is being carried out at the Max Planck Institute for Evolutionary Genetics, Plön, Germany, in collaboration with Diethard Tautz.
Studying the nature of variation from new spontaneous mutational variation in microbes can be done much more quickly than in mammals and done on a much larger scale. We have carried out mutation accumulation experiments in the single-celled algal species Chlamydomonas reinhardtii and its relative C. incerta and are using these to study of the nature of variation from spontaneous mutations, particularly their impact on traits related to fitness. This work is being carried out with Nick Colegrave (University of Edinburgh) funded by a grant from the BBSRC. By putting together information from precise measures of fitness traits with complete genome sequences of MA lines and crosses between MA lines and their ancestors, we can more directly infer properties of the distribution of fitness effects of mutations than has previously been possible.
The distribution of effects of deleterious mutations and rates and effects of advantageous mutations
The fixation of advantageous mutations leads to evolutionary adaptation, and populations are subject to a continual flux of deleterious mutations. In collaboration with Adam Eyre-Walker (University of Sussex) we have developed methods that use DNA sequence data from multiple individuals sampled from a population to infer the distribution of fitness effects of mutations, both deleterious with effects down to and neutrality, and those that are advantageous and contribute to adaptation. We are taking advantage of the vast amounts of new genomic sequence data that is becoming available on individuals sampled from populations of several species. Our methods have been widely applied by groups studying evolutionary genetics, and we are working on ways to generalise the kinds of models that can be fitted to data. An implementation of our method, DFE-alpha, is available under the software link.
The evolution of recombination and sex
We have used computer simulations to study a fundamental problem in evolutionary biology – why does sex and recombination exist? With Sally Otto (Univ. British Columbia) we showed that selective interference between linked deleterious mutations favours mutations that increase recombination (recombination modifiers), and that the advantage of recombination increases, apparently without limit, as population size increases. Since all real populations in nature are very large (at least those that stand a chance of persisting in the long term), this can therefore provide a general explanation for the evolution of recombination and can go some way towards explaining the evolutionary maintenance of sexual reproduction. We also studied the evolutionary maintenance of obligate sexual reproduction, a phenomenon for which a robust, general explanation has been more elusive.