Population genomics of Daphnia: mapping the 'arms-race genome'

We aim to measure the impact of conflict on the way genomes evolve. For example, what fraction of the differences between two genomes are a consequence of the arms-race between hosts and parasites? Is it a tiny amount, or do such conflicts dominate evolution at the molecular level? There is already some evidence that immune-system genes do show high rates of evolution, but it is not clear how general the effect is, or how big it is compared to other causes. We will answer this question by comparing the evolution of genes involved in host-parasite interaction (potential 'arms-race' genes), to the evolution of other genes. We will do this using the genome of an ecological and evolutionary model species - the water flea (Daphnia magna).

It is only possible to address such questions by studying many genes simultaneously - i.e. whole genomes. Until recently, such an approach was untenable: a 'genome project' was complete when it had sequenced the genome of a single individual. Now, new advances in technology make it possible to examine full genome sequences for tens (or even hundreds) of individuals, and the price has fallen to the point at which such 'population genomic' studies fall well within the range of a single project.

Daphnia are small freshwater crustaceans found in ponds throughout the UK and the world. Daphnia are well studied in terms of their ecology, so we know a great deal about the diversity of Daphnia and how this diversity arises when they interact with their environment. For example, Daphnia are used to assess the ecological impact of toxins in the environment; they adapt physiologically to a wide range of pH, food, oxygen, and temperature variation; and they exhibit specialised behaviour or morphology in response to predators. Daphnia are also interesting from a genetic perspective, for example they alternate between sexual and asexual reproduction, and they have nearly 50% more genes than humans - possibly because they have evolved to respond to such a wide range of environmental conditions. Most importantly for our study, Daphnia pathogens are widely studied in the lab and the field, so that we can identify which of their genes respond to pathogens, and to which pathogens those genes respond.

We will sequence the genomes of 50 Daphnia magna from ponds all across Europe, and after sequencing, we will use statistical methods based on population-genetic theory to ask how important conflict is in determining the genome-wide rate of adaptive evolution. Our data will be made freely available to everyone, both academics and the public, over the web. This will provide a vital resource for interpreting population-genomic studies in laboratory organisms, such as the fruit fly (Drosophila). It will also provide a spring-board for future genetic studies of ecology, conservation, epidemiology and ecotoxicology that use Daphnia as a study system.

As pure research, the direct impact of this study will be felt most strongly within the academic community and many of the potential indirect impacts (as outlined below) will come about through future research and development carried out by academic researchers. However, as this proposal addresses the evolutionary consequences of infection and disease, and relates the selective pressure imposed by parasites to features of the host's genome, it will impact:

(1) The natural environment: Small invertebrates such as Daphnia are ecologically important, and Daphnia is a key model for ecotoxicology. Therefore, by better understanding the environmental forces which have driven the evolution of the Daphnia genome, we will better understand the responses of such organisms to environmental challenge.

(2) The public: First, because the implications of this research relate to parasites and to disease, over the longer term it has the potential to shape biomedical research and clinical policy in ways that will improve quality of life for the public (see commercial applications, below). Second, because the evolutionary consequences of host-parasite conflict are intuitive and easy to convey to the non-specialist, projects such as this have strong potential to engage the public in a better understanding of their own genomes, and of genetics more generally.

(3) The commercial private sector: Daphnia constitute the best-studied model crustacean, and much of what we learn about the evolutionary consequences of parasites and disease for its genome are likely to generalise to commercially important crustaceans such as edible shrimps, crabs and lobsters, and also to fish 'lice' which constitute a major source of loss in the aquaculture industry. More generally, inherited genetic variation in disease susceptibility is a fundamental aspect of applied genetics which bears on human health (e.g. personalised medicine) and also diseases of livestock and agronomically important insects and plants

We will maximise the impact of this research by ensuring the widest possible dissemination of our results and analyses to the interested parties. To this end, we will: (i) publish our research in open access formats to enhance access for academics in distantly related fields, for academics in less developed countries, and for interested members of the public; (ii) make our data freely available online prior to publication; (iii) provide press releases in association with our primary general-interest results; and (iv) directly interact with policy makers in relevant field (e.g. ecotoxicology, conservation).