Evolution of antigen repertoires - Jay Taylor
Parasites that cause chronic infections in vertebrates use a variety of strategies to evade the adaptive immune responses of their hosts. One strategy, called antigenic variation, plays an important role in some vector-transmitted diseases and occurs when the parasite genome encodes multiple surface antigens, only a few of which are expressed at a time. Although host immune responses will eventually develop against expressed antigen types, the infection can persist if small numbers of parasites are able to randomly switch expression to antigen types that have not yet been seen by the host. Familiar examples of human pathogens that engage in antigenic variation include the bacterium Borrelia hermsii, which causes tickborne relapsing fever, and the parasitic protozoa Trypanosoma brucei and Plasmodium falciparum, which cause African sleeping sickness and malaria, respectively. Although genome sequencing projects are providing important insights into the makeup of antigen gene repertoires, little mathematical theory has been developed to understand how these gene families evolve. In part, this is because diversication of antigen repertoires depends on a hierarchy of processes operating at three levels. Within each parasite genome, the antigen repertoire is subject to mutation, recombination, gene conversion, and duplication or deletion of entire genes. This leads to variation between antigen repertoires which is subject to natural selection and demographic stochasticity both within individual infections as well as during transmission between hosts. The aim of this project will be to formulate a stochastic model that incorporates these genomic and epidemiological processes and to use simulations to investigate some of the following questions: (1) Why is there so much variation in the size of antigen repertoires (which range from a few dozen vlp and vsp genes in B. hermsii to more than a thousand vsg genes in T. brucei)? (2) Is pseudogene formation an inevitable consequence of neutral processes and delayed gene expression or can it be selectively advantageous to the parasite? Depending on the interests of the students, exploration of the model could be combined with a comparative study of antigen gene repertoires across dierent parasites.
Adaptation to environmental change in heterogeneous landscapes - Jay Taylor
One of the key unresolved issues in evolutionary genetics is the nature of the genetic variation that underlies adaptive evolution. When populations adapt to new environmental conditions, do they do so with mutations that arose prior to the environmental change, i.e., through standing variation, or must they wait for the appearance of novel mutations that are adapted to these conditions? Does adaptation primarily occur through the xation of a series of mutations of small effect, or will a few mutations of large effect suffice? Questions like these have received much attention in recent years, thanks in part to the increasing availability of population genomics data. However, much of the theory that has been developed to try to address these issues has ignored the role that might be played by spatial environmental variation. For example, as mean temperatures increase due to climate change, we might predict that species whose ranges extend into warmer regions will see the spread of warm-adapted mutations out of these regions. The aim of this project will be to use a combination of computer simulations and theory to explore these kinds of questions.