Evolutionary analyses of Plasmodium genomes

Abstract

Plasmodium is the genus responsible for causing malaria in humans, killing more than 400,000 individuals a year. Species from the genus are also capable of infecting different primate, avian and rodent species. In this thesis I use previously published genomic data to investigate several aspects of Plasmodium evolution. I compare mutation rates and the strength of selective constraint across different subgenera of Plasmodium. I find little to no conservation of mutation rate across the genus, and no evidence that these mutation rate changes are driven by selective optimisation. I analyse patterns of polymorphism in human-infecting and ape-infecting Plasmodium species, looking for signatures of natural selection. Using this data, I find evidence for a breakdown in the efficacy of purifying selection in the recent evolutionary history of human-infecting species, but not in ape-infecting species. I suggest this breakdown is caused by recent population expansions in the humaninfecting populations. I investigate different methods to study the historic selective regime of individual genes without being confounded by this recent breakdown in the efficacy of purifying selection. I find strong evidence for ongoing GC biased gene conversion in human-infecting Plasmodium vivax from polymorphism patterns, and find evidence for this process in the evolutionary history of species from other subgenera. I suggest the differential strength of this process across the genus is responsible for the wide range of genome GC contents found across different Plasmodium species. Additionally, using the same polymorphism data, I find little evidence for ongoing selection on codon usage in Plasmodium falciparum.