Projects

1. HIV Adaptive Dynamics

The adaptive dynamics of HIV-1 at the molecular population genetic level are being studied through simulation modelling. Reliable estimates of fundamental population genetic parameters for HIV-1 allow the realistic simulation of the molecular evolution of a virus population infecting a patient. The main obstacle to simulating adaptive evolution is knowledge of the site-specific marginal fitness effects of amino acids. We have recently described a relationship between mean amino acid site-specific frequency and the site-specific fitness effect of an amino acid for the intensely studied V3 region of the HIV-1 exterior envelope glycoprotein, gp120. This will allow us to test models of molecular adaptive dynamics and to examine the factors affecting the rate and limit of adaptation of HIV-1 to target cells and immune surveillance.

2. The Rate Curve for Molecular Evolution

A recent analysis of mtDNA sequences from vertebrate taxa has shown that the rate of evolution decreases with increasing time since divergence between taxa. We are testing this pattern with serially sampled ancient DNA sequences from bison, cave bears, and penguins and with HIV-1 sequences serially sampled from patients. We are also developing the theoretical basis for this pattern. This work is being done in collaboration with Professor Alan Cooper of the School of Earth and Environmental Sciences.

3. Codon Bias and the Evolution of MHC Genes in Xiphophorus Fishes (Swordtails)

Elevated rates of synonymous nucleotide substitution in protein coding genes are difficult to explain because these substitutions are not directly influenced by selection at the protein level. However, it has been proposed that a combination of positive selection and codon bias may elevate both nonsynonymous and synonymous rates. This hypothesis will be tested with sequences from the class II MHC gene DAB from two species of Xiphophorus fishes. This gene exhibits elevated levels of both nonsynonymous and synonymous substitution in the beta-1 encoding exon, but not in other protein coding regions. In this study, a combination of molecular systematics and simulation modelling will be used to determine whether positive selection of the beta-1 domain and subsequent selection for preferred codons explains the elevated synonymous substitution rate. This is a collaborative project with Drs. Kyle Summers and Tom McConnell at East Carolina University, USA.

4. Interorganellar Transposition of DNA

The movement of DNA between organelles is established as a major driving force in eukaryotic evolution. We have established experimentally that DNA moves frequently from the plastid (chloroplast) genome to the nucleus. The main aims of this project are to determine the mechanism of transfer and to measure the frequency of transposition of DNA from the plastid to the mitochondrion. This is being investigated using the Chlamydomonas and tobacco systems in collaborationn with Professor Jeremy Timmis.