Role of eukaryotic Sel-1 like repeat containing genes in Helicobacter pylori evolution and pathogenesis.
Date on Master's Thesis/Doctoral Dissertation
Committee Co-Chair (if applicable)
Perlin, Michael H.
Perlin, Michael H.
Berg, Douglas E.
Kwaik, Yousef Abu
Helicobacter pylori; Co-adaptation; Evolution; Pathogenesis; "slr" genes; Virulence
Helicobacter pylori--Molecular genetics; Helicobacter pylori infections
Background: Helicobacter pylori (Hp) establishes life-long gastric infection in billions of humans, and is often responsible for diseases such as peptic ulcer and gastric cancer. Cumulative actions of genetic drift and natural selection over several millennia sculpted the present Hp population structure, which is characterized by extreme genetic diversity and striking geographic clustering of genotypes. Natural selection is more commonly imprinted in DNA sequences of Hp proteins that interact with host components; however, in most instances biological relevance of selection during Hp infection remains unknown. Here, I attempted to elucidate the consequence of natural selection in two different contexts: (1) on the preservation of duplicated genes in Hp genome; and (2) lineage-specific adaptive evolution in Hp virulence protein HepC. Principle Findings: I characterized the molecular evolutionary dynamics of paralogs, hcpC and hcpG, which belong to the Hp Sell-like gene family. hcpG genomic analyses identified three distinct states in natural Hp populations, whereby hcpG was either deleted, pseudogenized or encoded highly polymorphic alleles. In contrast, full-length hcpC alleles were conserved in all genomes. Although positive selection was detected in the phylogenies of hcpG and hcpC indicating that both genes had evolved under pressure to diversify, the intensity of selection was much stronger on hcpG than hcpC. The contribution of hcpC to Hp fitness, in the AGS cell culture infection model, was significantly greater than hcpG; however, both genes together demonstrated an additive effect on Hp fitness during infection (24 hrs pj.: S.1hcpc= 0.264 vs. S.1hcpG= 0.074, P
Putty, Kalyani, "Role of eukaryotic Sel-1 like repeat containing genes in Helicobacter pylori evolution and pathogenesis." (2010). Electronic Theses and Dissertations. Paper 1169.