Lateral genetic transfer (LGT) is the movement of genetic material across, rather than within, lineages. This process occurs through phage transduction, natural transformation, or conjugation, and is particularly notable in the spread of determinants for antibiotic resistance and other important adaptive traits among prokaryotes. Successful LGT consists of a succession of steps: the physical uptake of foreign DNA into a host new cell; recombination into the genome; subsequent integration into native cellular networks; and finally, establishment in the population. Each of these steps presents differential opportunities and barriers that dynamically construct genetic exchange communities (GECs). The routes by which bacteria take up and recombine foreign DNA are now adequately known; however, characterization of systems-level factors that govern interplay among donor and recipient lineages in dynamic environments remains a challenge. The principal aim of this thesis was to integrate rigorous phylogenetic and network analyses to identify properties of evolutionarily successful LGT. All analyses are focused on the important and well- studied Escherichia coli – Shigella group of enteric bacteria.
Chapter Two presents a comprehensive review of how each step in lateral transfer from genetic recombination and regulatory integration, to establishment in the host populations offers opportunities for the construction of GECs. A set-based definition, as well as a review of the features of actual GECs is presented. This set-based formulation provides a basis for addressing questions regarding the biases and frequencies of transfer that construct GECs. Chapter Three presents data showing that E. coli – Shigella GECs are shaped principally by phylogeny, rather than by ecology or lifestyle, with most gene exchange occurring between close relatives. This bias extends not only to intact genes, but also to gene fragments.
In the following chapters the focus is narrowed to examine the integration of laterally acquired genetic material and corresponding gene products with host transcriptional and post-transcriptional regulatory networks. Chapter Four details broad trends that govern system-level integration of laterally acquired genetic material with transcriptional regulatory networks. Data are presented showing that neighbour regulators (genes which regulate adjacent genes on the chromosome) have higher frequencies of transfer than global regulatory genes, implicating the connectivity of regulatory genes in transcriptional networks as contributing to successful LGT. Likewise, Chapter Five links the connectivity of genes and sRNAs in post-transcriptional regulatory networks to their evolutionary dynamics within the clade. Intriguingly, the majority of genes targeted by sRNAs and the sRNA chaperone protein Hfq have been transferred intact within the E. coli – Shigella clade, suggesting that Hfq and sRNAs help integrate laterally acquired genes into established regulatory networks. This potentially represents an important mechanism by which bacteria limit the costs of inappropriate expression of laterally acquired genes. This thesis concludes with a general discussion of the implications of these findings, for a more-integrated understanding of LGT across the microbial biosphere.