Effects of metapopulation structure and recombination on bacterial populations

Abstract

Bacteria are subject to a wide variety of complementary and competing forces which work to shape the populations observed in the natural world. In the case of bacterial pathogens, epidemiological factors play a significant role in the evolution of a pathogenic species, and the relatively low diversities observed on a global scale in significant pathogens may be due to the phenomenon of a microepidemic population structure, operating in concert with homologous recombination and mutation. In this work I explicitly define the microepidemic population concept in population genetics terms, and examine its consequences for pathogen population structure and inference of population characteristics from data. I make use of simulated metapopulations to model simplified populations composed of neutral microepidemics in order to examine the varying effects of homologous recombination and mutation in pathogens. The analysis is then extended to include different kinds of selection, both at an individual level and at a metapopulation level, to investigate the consequences of these processes, and to contrast with the results from neutral populations. With the increasing number of resources containing large, globally sampled strain collections, I also examine the effects of metapopulation structure on population genetic methods of analysis which have been applied to bacterial datasets (including Gst, the Neutral Microepidemic Model, and IA). Using simulated populations I consider these methods in light of database limitations such as those arising from the longitudinally sampled nature of the collections, and those introduced by geographic over- and undersampling. This is followed by an examination of the effectiveness of some of the methods using sequence data (phylogenetics, BAPS and ClonalFrame) which are commonly employed to ask questions relating to population structure. The work concludes with the application of these methods to examine the population genetics of several bacteria of interest.