The Jiggins Lab Webpage

Research

Genetic variation in susceptibility to parasites

In many organisms there is a lot of genetic variation in the susceptibility of individuals to parasitism. Yet this appears paradoxical. Being resistant is clearly advantageous, so why hasn't natural selection eliminated the susceptible alleles from the population? We are attempting to identify the genes and mutations that cause this variation in wild Drosophila populations. This will allow us to understand both the molecular causes of this variation, and ultimately the evolutionary reasons why natural selection hasn't eliminated susceptibility alleles from the population.

To tackle this question we have primarily been using the sigma virus, a vertically transmitted Rhabdovirus that is a specialist on Drosophila melanogaster. We have also worked on several species of parasitoid wasps, all of which are major causes of death in wild fly populations and the fungal pathogen Beauveria bassiana which is a generalist insect pathogen. In all cases, we have found that there is a remarkably large amount of variation in the resistance of Drosophila in wild populations (Figure 1). We have then gone on to map regions of the genome (QTL) that contain major effect genes causing this variation. We have narrowed down the location of several of these loci to regions of the genome containing just a few genes and are in the process of identifying the specific nucleotides involved.

Figure 1. The rate of sigma virus transmission by fly lines that differ only in second chromosomes that were sampled from the wild. Some of this variation is caused by a polymorphism in the ref(2)P gene.

The evolution of immune systems

Host-parasite interactions are commonly associated with rapid evolution. This occurs because hosts are continually evolving novel defences, while parasites evolve to evade those defences. We have been using the signature that natural selection leaves in their pattern of molecular evolution and DNA sequence variation to infer the selection pressures acting on different components of the immune system.

Which components of the immune system coevolve with parasites? Surprisingly, we found that proteins that interact directly with microbial pathogens, such as pattern recognition molecules and antifungal peptides, often evolve very slowly. However, in collaboration with Darren Obbard and Tom Little, we found that natural selection causes the antiviral RNAi genes evolve extremely fast (Figure 2). This may be driven by selection to evade viral suppressors of the fly's RNAi defences.

The second question we have addressed is the type of selection pressures acting on immune systems. Although many theoretical models of host-parasite coevolution predict that natural selection will maintain polymorphisms within populations, we have yet to see any evidence of ancient polymorphisms in the Drosophila immune system. Instead, beneficial mutations arise in many immunity genes and sweeping fixation. This supports the idea that hosts and parasites are engaged in an arms race, in which adaptations in the parasite population are matched by novel counter-adaptations by the host.

Figure 2. Rapid evolution in immune-related genes. The genes are coloured according to the rate of adaptive substitution (the number of adaptive substitutions per non-synonymous site between D. melanogaster and D. simulans). Red indicates genes in which natural selection is causing high rates of adaptive evolution.

Viral pathogens

Despite the Drosophila immune system being widely studied by immunologists, we know remarkably little about its natural pathogens. Therefore, we have been investigating the ecology of Drosophila viruses. The sigma virus is the only host specific pathogen isolated from D. melanogaster populations, and we find that it typically infects a few percent of wild flies. We have recently found two new sigma viruses in different species of Drosophila, and found that they probably form a new genus of rhabbdoviruses (Figure 3).

Figure 3. Phylogeny of the rhabdoviruses showing that the sigma viruses form a major new group.

Mosquitoes

Insect vectored diseases are of considerable medical importance, and we are working on one of the most important vector species, the mosquito Aedes aegypti. We are interested in the enormous amount of genetic variation within populations of A. aegypti in the ability to transmit human pathogens. We are resequencing the genomes of several lines of Aedes aegypti to characterise both structural and sequence variation in their genomes, and characterising the transcriptome of A. aegypti for the first time using RNA-Seq technology. We are also looking at genetic variation in the ability of mosquitoes to transmit the human parasite Brugia malayi, which is a cause of lymphatic filariasis. This work is in collaboration with Arnab Pain who is based at KAUST in Saudi Arabia.

Figure 4. Aedes aegypti (Source: CDC).

Myxoma virus

The introduction of the myxoma virus into populations of rabbits in Europe and Australia caused massive mortality, and imposed strong selection for increased resistance in the rabbit population and reduced virulence in the virus population. In collaboration with researchers in CIBIO, Portugal, we are using next-generation sequencing to understand the genetic basis of the evolutionary changes that occurred in the host and parasite populations over the 55 years since the virus was released.

Figure 5. European Rabbits (Source: Wikimedia Commons).