Evolution of viruses, and evolution of bacteria. My research employs computer analyses of nucleotide and protein sequence data to address a range of evolutionary questions.
Viral evolution: what are the origins of human viruses, and what factors influence their genetic diversity? A particular focus has been the origins and evolution of AIDS viruses.
Bacterial evolution: what do bacterial genome sequences tell us about evolution? Two particular areas involve the evolution of synonymous codon usage bias, and the evolution of repetitive sequence families.
Amplification of DNA sequences from non-invasive (faecal) samples has revealed that chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) are each infected with three host-specific Plasmodium species from the subgenus Laverania, which also includes P. falciparum, the cause of malignant malaria in humans. Phylogenetic analyses show that P. falciparum arose from cross-species transmission of one of the gorilla parasites, but that this jump has occurred successfully on only one occasion.
We are now studying the genome sequences of these ape parasite species in order to understand the evolution of the Laverania as a whole, and to shed light on the cross-species transmission from gorillas to humans. We have used selective whole-genome amplification to obtain near-complete genome sequences from one strain of P. reichenowi (a close relative of P. falciparum) and two strains of P. gaboni (a more divergent member of the Laverania), directly from samples from naturally infected wild chimpanzees. We have compared these sequences to a recently published genome from the only laboratory isolate of P. reichenowi, and to data from multiple strains of P. falciparum. The two chimpanzee parasite species show levels of within-species diversity about 10 times higher than seen among P. falciparum strains from across Africa and Asia, consistent with the human parasite having undergone a very recent population bottleneck during transmission from gorillas. Comparative analyses also reveal that a segment of chromosome 4 has undergone horizontal gene transfer (HGT) from a close relative of P. gaboni into the gorilla parasite that was the ancestor of P. falciparum. The transferred genes include that encoding RH5, which appears essential for erythrocyte invasion by P. falciparum, and we speculate that sequence change resulting from HGT may have been important in the process by which the precursor of P. falciparum acquired the ability to infect humans.