Date of Award
Department or Program
Ecology, Evolution, Environment and Society
The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve as a part of their host genomes. In this work, we extensively analyze evolutionary patterns of alphaproteobacterial GTAs using comparative genomics, phylogenomics and machine learning methods. We initially develop an algorithm that validate the wide presence of GTA elements in alphaproteobacterial genomes, where they are generally mistaken for prophages due to their homology. Furthermore, we demonstrate that GTAs evolve under the selection that reduces the energetic cost of their production, indicating their importance for the conditions of the nutrient depletion. The genome-wide screenings of translational selection and coevolution signatures highlight the significance of GTAs as a stress-response adaptation for the horizontal gene transfer, revealing a set of previously unknown genes that could play a role in the GTA cycle. As production of GTAs leads to the host death, their maintenance is likely to be under a kin or group level selection. By combining our findings with accumulated body of knowledge, this work proposes a conceptual model illustrating the role of GTAs in bacterial populations and their persistence for hundreds of millions of years of evolution.
Kogay, R., Neely, T. B., Birnbaum, D. P., Hankel, C. R., Shakya, M., & Zhaxybayeva, O. (2019). Machine-learning classification suggests that many alphaproteobacterial prophages may instead be gene transfer agents. Genome Biology and Evolution, 11(10), 2941-2953.
Kogay, R., Wolf, Y. I., Koonin, E. V., & Zhaxybayeva, O. (2020). Selection for reducing energy cost of protein production drives the GC content and amino acid composition bias in gene transfer agents. Mbio, 11(4), 10-1128.
Kogay, R., & Zhaxybayeva, O. (2022). Selection for translational efficiency in genes associated with alphaproteobacterial gene transfer agents. Msystems, 7(6), e00892-22.
Kogay, R., & Zhaxybayeva, O. (2023). Co-evolution of gene transfer agents and their alphaproteobacterial hosts. bioRxiv, 2023-08.
Kogay, R., Koppenhöfer, S., Beatty, J. T., Kuhn, J. H., Lang, A. S., & Zhaxybayeva, O. (2022). Formal recognition and classification of gene transfer agents as viriforms. Virus Evolution, 8(2), veac100.
Kogay, Roman, "Tracing Evolution of Gene Transfer Agents Using Comparative Genomics" (2023). Dartmouth College Ph.D Dissertations. 165.