- Evolutionary Medicine
Research objectives in this area centre on three broad topics: (A) the evolution of pathogen virulence, (B) the control infectious diseases and drug resistance, and (C) the evolution of senescence.
(A) Evolutionary theory is challenging the deeply entrenched notion that successful pathogens eventually evolve toward benign coexistence with their hosts. Emerging theory and experimental data have revealed that the degree of evolved virulence (defined as parasite-induced host mortality) depends on the ecology of both host and parasite. The challenge for theoreticians and empiricists is to discover the specific factors that direct virulence evolution. Our group is currently exploring a number of open theoretical questions in this area, including questions involving the quantitative genetics of virulence evolution, virulence evolution in multi-host and more realistic ecological settings, and virulence evolution in spatially structured populations. A monograph on evolutionary epidemiology is currently underway with Sylvain Gandon for Oxford University Press.
(B) The evolution of drug resistance is one of the most challenging problems facing modern medicine. Every time a new antimicrobial drug has been introduced to control an infectious disease, resistance to the drug has eventually evolved. We are exploring how ideas from evolutionary biology might be used to better control (and perhaps even prevent) the emergence of drug resistance. We use mathematical models to predict how best to use drugs at both the population and the individual level. Currently our results suggest that some modern practices are probably not optimal from an evolutionary standpoint. We are also developing theory to explore how multiple chemical agents might be used to slow the evolution of resistance. A new project is looking at the very same issues in the context of resistance to cancer chemotherapy.
(C) Senescence is the deterioration in reproductive potential of an organism as it ages. There are two main hypotheses for the evolution of senescence, the mutation accumulation (MA) hypothesis, and the antagonistic pleiotropy (AP) hypothesis. The MA hypothesis asserts that age-specific deleterious mutations reach a higher frequency for later ages as a result of the declining strength of selection. The AP hypothesis asserts that there is a trade-off between reproductive success early and late in life. Since the strength of selection declines with age, early reproduction is favoured at the expense of late. These theories have been treated largely as alternative hypotheses, but evidence for both is often found. We are currently exploring models that examine the interplay between these two hypothese as well as models that explore the evolution of senescence in more realistic ecological settings.
- Epigenetic and Nongenetic Inheritance
Inheritance -- the influence of ancestors on the phenotypes of their descendants -- translates natural selection into evolutionary change. For the past century, inheritance has been conceptualized almost exclusively as the transmission of DNA-sequence variation from parents to offspring in accordance with Mendelian rules. Recent advances in cell- and developmental biology, however, have revealed a rich array of other inheritance mechanisms that exist alongside DNA. These include patterns of methylation, RNA inheritance, and other still as yet undiscovered biochemical processes. We are using mathematical tools such as the Price equation to develop a unified theoretical approach for understanding the evolutionary consequences of nongenetic inheritance. Our group also builds specific models to examine how things like transposable elements and RNAi might mediate novel patterns of inheritance. A monograph on the subject is currently underway with Russell Bonduriansky for Princeton University Press.
- Sexual Conflict/Sexual Selection
Both males and females of many species have evolved surprisingly intricate characteristics that appear to be involved in sexual interactions between the two. Much of the current thinking about how such traits evolve is based on the premise that there is an evolutionary conflict of interest between the two parties over many aspects of mating and reproduction.
Over the last few years several papers have been published that contain data bearing on these issues, but as yet there is still no complete quantitative theoretical framework in which to interpret these results. Consequently, there are conflicting opinions about what we should expect to observe under different evolutionary scenarios.
We are developing theoretical models aimed at predicting the outcome of coevolutionary interactions between males and females. We are also constructing theory that explores a number of related issues with the field of sexual selection, including the effects of spatial population structure, and the interplay between orgnismal life history patterns and evolution, and the evolution of male secondary sexual characters. A related project will also focus on drawing out the theoretical connections between various models of sexual selection and the theory of sexual conflict.
- Genomic Conflict and Imprinting
One of the most intriguing types of evolutionary conflict documented occurs at the genome level. It need not be the case that different loci within a genome, or even different alleles at the same locus within a genome be acted upon in the same way by natural selection. For example, there is now good empirical evidence and theory suggesting that natural selection acts differently on alleles depending upon their parent of origin. In some cases this conflict appears to have resulted in the evolution of differential allelic expression depending upon whether the allele was inherited maternally or paternally (genomic imprinting). Although a strong body of theory has been developed to explain this specific phenomenon, the evolutionary processes involved are actually very general.
We are using the mathematical tools of kin selection to construct a more general theory of genomic conflict to understand how the form of genomic conflict that has resulted in the evolution of imprinting is related to other evolutionary conflicts. This theory is intended to illustrate how conflict between alleles owing to their 'parent of origin' is a special case of a much more general phenomenon of evolutionary conflict between different 'classes' of alleles.