An integrated approach to genome evolution using the Drosophila model

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Developed over the past hundred years, 'population genetics' (the study of how genes and genetic material are inherited in populations) has provided a rigorous mathematical basis for evolutionary theory. More recently, as genome-scale DNA sequencing has moved from being merely possible to routine, 'population genetics' has become 'population genomics', and our power to link theory with data has grown beyond the wildest dreams of early evolutionary biologists. We now, almost routinely, have access to hundreds or even thousands of genomes -- at least from a few key species such as humans, mice, and the classical laboratory fruit fly, Drosophila melanogaster. These data allow us deep insight into the mechanisms of genome evolution in these species, and start to allow us a general picture of the way genomes evolve.From a genetic perspective, theory says that -- when single populations are considered -- four processes matter. These are mutation, which creates new variants in the population, recombination, which creates new combinations of variants, natural selection, which determines whether variants become more common or are lost from the population, and genetic drift, which describes how variants change in frequency when selection is weak or absent. By estimating the rates at which each of these processes occur, how they vary within genomes and among species, and how they correlate with each other, we can ultimately hope to provide a complete genetic view of genome evolution.However, while there are good estimates for some rates (such as recombination rate) from many species, and good estimates of all rates from a very few species, there is no group of related plant or animal species for which all rates have been estimated. In particular, there are very few direct experimental estimates of mutation rate from plants or animals, so we have little idea of how this varies among species or how it correlates with the other processes. Our research aims to fill this gap in our knowledge by quantifying all four processes in a single set of 23 related Drosophila species. The most recent ancestor of these flies lived more than 30 million year ago, the species come from all over the world, and they vary in their size, what they eat, how long they live, their optimum temperature, and even how susceptible they are to disease. What they have in common is that we can breed them in the lab, and that we already know enough about their biology to benefit from studying it further. In this project we will directly estimate mutation and recombination rates and how they vary within and among species, and we will use population-genetic theory to indirectly estimate the strength of selection and the long-term rate of genetic drift. We will do this by sequencing 7 genomes (two parents and 5 offspring) from 5 families from each of the 23 species of Drosophila. We will directly identify new mutations and new recombination events that are present in the offspring but absent from their parents to estimate the rate that these processes occur. Then, using the parental genomes (and incorporating information from the offspring), we will use indirect (population-genetic) methods to infer the historic strength of selection and rates of genetic drift. These data will allow us to describe genome evolution in this group of important and well-studied species more completely that ever before. And, by doing this, we will not only gain a better understanding of the evolutionary process, but also provide data to further test theory and drive its ongoing development. Our data will also be available to many other researchers for future work on other topics, beyond this proposal.