New insights into the regulation and evolution of gene transfer agents in Alphaproteobacteria through comparative genomics and transcriptomics

Koppenhöfer, Sonja Elena (2022) New insights into the regulation and evolution of gene transfer agents in Alphaproteobacteria through comparative genomics and transcriptomics. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Gene transfer agents (GTA) are phage-like particles that can transfer fragments of the host genome between cells. GTAs are particularly widely distributed in the Alphaproteobacteria where their expression is controlled by their hosts gene regulatory network in the model organisms. In this thesis, I used computational comparative analyses of publicly available datasets to further extend our knowledge about the regulatory networks controlling GTA production and to identify genomic traits that might help explain the strong conservation of GTAs in these bacteria. Reanalysis of transcriptomic datasets revealed a regulatory interplay between nitrogen- and oxygen-sensing regulators with the CtrA phosphorelay, which is an established regulator of GTA gene expression. I evaluated the chromosomal locations of genes encoding GTA regulators, components of the CtrA phosphorelay, and enzymes associated with the synthesis and degradation of the GTA-affecting second messenger c-di-GMP. These showed some conserved distribution patterns along the chromosome, which might indicate that GTA production is coordinated with the cell cycle. Finally, I showed that GTA genes share many properties with core genes, such as the preferred location on the leading strand, in low plasticity regions and in GC skew peaks. Overall, the results of my dissertation provide novel insights for understanding the regulation of GTA gene expression and the evolution of the GTA gene cluster in Alphaproteobacteria and revealed several potentially important aspects that can be followed up on in the future with experimental studies to test their relevance to GTA biology.

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