Quantifying Adaptive Evolution in the Drosophila Immune System

It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, but the nature of the selection pressure driving this evolution remains largely unknown. As organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a cause of adaptive molecular evolution. To quantify this effect, and to identify which genes and pathways are most likely to be involved in the host-parasite arms races, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. The rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host-parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. We believe these are the first quantitative estimates of the role that natural selection plays in the evolution of the immune system, and they demonstrate that adaptation to parasites is an important force driving molecular evolution.