Lateral gene transfer (LGT) is an important force in bacterial evolution and adaptation. Bacterial species employ a variety of LGT mechanisms to exchange genetic information, including transduction, conjugation, and natural transformation. Using whole genome sequence data from several bacterial pathogens, I found that distributive conjugal transfer (DCT), a mechanism of LGT originally described in Mycobacterium smegmatis, produces distinct genomic signatures, including larger tract size and less biased tract location, compared to other mechanisms. Additionally, I showed that the likely mechanism in Mycobacterium canettii is DCT. Given the phylogenetic relationship of M. smegmatis and M. canettii, DCT may be a conserved mechanism for LGT across mycobacterial evolution.

DCT in M. smegmatis is regulated by type VII secretion systems (T7SS) encoded by ESX loci. Mycobacterial species encode 2-5 chromosomal copies of ESX loci, and T7SS involved in mycobacterial plasmid conjugation were also recently described. In order to gain further insight into the evolution of this LGT-associated machinery, I identified ESX loci in mycobacterial chromosomes and plasmids. All chromosomal ESX lineages were associated with a basal plasmid lineage, and a plasmid origin for ESX is the most parsimonious explanation for the phylogeny. Each chromosomal T7SS plays a distinct role in mycobacterial biology, and I found that positive selection during diversification on plasmids, migration to the chromosome, and speciation of mycobacteria contributed to this functional divergence.

Identifying genes under positive selection in bacterial pathogens is important to understand their evolution and adaptation to human hosts. Many population genetics statistics to measure diversity and selection from genomic data were developed for sexual species, where recombination occurs by crossing over during meiosis. Using whole genome sequence data from the recombining pathogen Staphylococcus saprophyticus and the clonal pathogen Mycobacterium tuberculosis, I identified methods to describe positively selected loci in bacteria. I discovered the first single nucleotide selective sweep in a bacterial species in the fibronectin binding domain of Aas in S. saprophyticus. I also contributed to a better understanding of the genetic architecture of drug resistance in M. tuberculosis, finding that selection leaves distinct population level signatures based on the size of the genetic target for resistance.