|Ph.D Student||Bolotin Evgeni|
|Subject||Evolution of Gene-Content Variation in Bacterial Genomes|
|Department||Department of Medicine||Supervisor||Professor Ruth Hershberg|
Bacterial species exhibit extensive variation in their gene repertoires. Two main processes are responsible for creating this variation: gene loss and gene gain. While the molecular mechanisms generating gene content variation in bacteria are relatively well understood, the evolutionary dynamics that underlie this variation remain unclear. In my thesis research, I developed and utilized a pangenome-based method to identify and separate instances of gene content variation stemming from gene loss and gene gain. I utilized this method to study the dynamics of gene loss and gain across multiple bacterial species and distinct environments.
I started my research by analyzing and comparing sources of genetic variation between non-clonal bacterial species, which undergo extensive horizontal gene transfer (HGT) and recombination, and clonal bacterial species that evolve in the absence or near absence of recombination and HGT. I found that, relative to low levels of sequence variation found within clonal species, gene loss is surprisingly frequent within these species. Gene content variation generated by gene loss appears to be the major source of genetic variation available for the evolution of clonal bacterial pathogens.
Next, I focused on investigating the dynamics of gene loss in a large collection of bacterial species. This enabled me to demonstrate that gene loss occurs in a largely clocklike manner within a pool of genes that were under weaker selection for their maintenance even before their loss. These results suggested that the majority of gene loss events are not explained by shifts in selection acting on the conservation of genes within the genome. Rather, genes seemed to be lost stochastically from a pool of genes that are consistently subject to weaker selection on their maintenance.
In the third study, I moved my focus to analysis of gene gain. I found that a surprisingly high proportion of horizontally acquired genes is shared between closely related species. Further, I demonstrated that frequently shared horizontally acquired genes differ in their characteristics from less ubiquitously shared horizontally acquired genes.
Finally, I examined how patterns of gene content variation within a single species relate to patterns of gene content variation across species and environments. I found that, to a very large extent, patterns of gene content variation within a single species recapitulate across species and diverse environments. These findings suggest that the majority of gene content variation is not explained by environmentally specific selection. Rather, across diverse environments, the same genes are found at similar frequencies, suggesting that their gain or loss is governed by similar selection across environments and by neutral evolutionary processes.
Combined, the results of my research demonstrate the importance of gene content variation for the evolution of bacterial species, and show that despite this importance, much of gene content variation is likely to be generated in a neutral rather than selective fashion.