The Jiggins Lab Webpage


Genetic variation in susceptibility to parasites

In most 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 identifying 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 been using linkage mapping and genome-wide association studies (GWAS) in investigate the genetic basis of virus resistance in Drosophila. In all cases, we have found that there is a remarkably large amount of genetic variation in resistance, much of which is explained by a small number of major-effect resistance polymorphisms (e.g. Figure 1). The genes causing this variation appear to encode both components of the fly's immune system, and other host factors that are hijacked by the virus to complete its replication cycle. Population genetic analyses suggest that in most cases the resistant allele of the gene has arisen recently and is currently sweeping through the fly population.

Figure 1. Successive increases in the resistance of Drosophila to viral infection have occurred through a transposon insertion followed by a duplication

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.

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 found that sigma viruses a common in a range of Drosophila species, and that they probably form a new genus of rhabbdoviruses (Figure 3).

Pathogens frequently jump between different host species, and this can result in the emergence of new infectious diseases such as HIV. We are using the sigma viruses as a model system to understand what factors allow pathogens to infect novel hosts and how viruses evolve to adapt to their new hosts by the host following a host shift.

Figure 3. Phylogeny of the the sigma viruses and their hosts (fly images: Nicolas Gompel).


Insect vectored diseases are of considerable medical importance, and we are working on two of the most important vector species, the mosquitoes Aedes aegypti and Culex spp. We are interested in the enormous amount of genetic variation within populations in their ability to transmit human pathogens, as well as factors affecting fitness and survival. We are resequencing the genomes of large samples of Aedes aegypti to characterise sequence variation in their genomes, and characterising the transcriptome of A. aegypti 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. We have excellent insectary facilities for infection and survival assays.

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).