טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSavkin Michal
SubjectCodon Usage Optimization and Horizontal Gene
Transfer via Bacteriophage Transduction
DepartmentDepartment of Medicine
Supervisor Professor Ruth Hershberg
Full Thesis textFull thesis text - English Version


Abstract

Horizontal gene transfer (HGT) is a mechanism responsible for much of the interspecies genetic diversity in bacteria. Genes can be acquired horizontally from other bacteria, from the environment or from bacteriophages. In order for genes to be maintained within the bacterial genome that has acquired them, they must not be toxic to the cell.  Acquired genes that display a strong mismatch to the codon usage patterns of their host cell may be toxic to the cell, and will not tend to be maintained. Genes from phages have been shown to be pre-adapted to the codon usage of their hosts. I therefore wanted to test the hypothesis that genes acquired horizontally from phages will tend to more often be maintained within their host species than genes acquired horizontally from other sources. Furthermore, I wanted to demonstrate that indeed genes acquired from phages match better the codon usage of their host, at the point of acquisition.

I used a pangenome-based approach to study the gene content dynamics of ten bacterial species that have been shown to undergo horizontal gene transfer to varying extents. This allowed me to predict which genes within each species are likely to have been introduced into the species via HGT. I was also able to identify genes that are more likely to have been introduced into each species less recently and therefore maintained longer. Next, I classified genes into phage and non-phage genes. To do so, I employed two classification methods: (i) product annotations from the strains’ genomic GenBank files; and (ii) PhiSpy, a program designed for detecting intra-genomic viral inserts.

I found that, fitting with my hypothesis, for the majority of the species examined in this study, genes acquired from phages were more successful at remaining and establishing themselves within the species’ genome compared to genes acquired from other sources. I further established that, compared to other recently acquired genes, recently acquired phage genes tend to display patterns of codon usage that better match those of their host bacterial species. Combined, these results suggest that pre-adaptation in codon usage patterns contributes to a higher likelihood of maintenance of genes acquired horizontally from bacteriophages.