Molecular arms-races and the evolution of immune genes
We are interested in understanding how gene function determines the rate of adaptive evolution, and particularly whether molecular 'arms-races' might drive a disproportionate amount of adaptive substitution. Because the immune system coevolves with pathogens (and other parasites), it is expected to evolve rapidly relative to the rest of the genome, and we have used population genetics approaches in Drosophila to look for differences in the rate of adaptive evolution between immunity and non-immunity genes, and between different types of immunity gene. In Drosophila it is striking that RNAi genes (including those that defend against viruses) show very strong evidence of adaptive evolution, suggesting that they are engaged in a host-parasite arms race with viruses. To understand whether this is peculiar to Drosophila, we are now asking similar questions using a population-genomic study of Daphnia magna, in collaboration with Tom Little.
Although Drosophila is one of our best models for innate immunity, until recently we have known surprisingly little about Drosophila's natural pathogens. Viruses are common in Drosophila and may be a major driver of evolution in its immune system. However, so far only a handful have been studied in the lab, and apart from the Sigma rhabdovirus (see The Jiggins Lab) none have been widely studied in the wild. We have used a metagenomic approach (RNAseq and siRNAs) to identify more than 20 new Drosophila melanogaster RNA viruses and a DNA virus in the wild. RT-PCR surveys of flies in the wild, and of publicly available RNAseq data from lab stocks and cell culture, suggest that many of these viruses may be common, and we are currently trying to isolate some of them for further study. We are also extending this study to several other species of Drosophila with the longer-term aim of understanding viral ecology in the Drosophilidae.
The evolution of RNAi
RNA interference has an essential role in mediating defence against viruses and transposable elements. This is well-studied in plants, nematodes and insects, and appears to be phylogenetically ancient. However, in the absence of experimental data from basal eukaryotes (and most animal phyla), the origins and homology between antiviral RNAi mechanisms remains unclear. We are therefore using a metagenomic approach to study viruses and virus-derived siRNAs in a range of non-model lineages. We also have a broad interest in the way that RNAi pathway genes evolve. This includes both the origins and duplication history of major RNAi gene families, and the role that seelction mediated by viruses and/or transposable elements might have played in shaping their sequences.