Genomic Diversity of Helicobacter pylori

Lee, Won Kon; Choi, Sang Haeng; Park, Seon Gyu; Choi, Yeo Jeong; Choe, Mi Young; Park, Jeong Won; Jung, Sun Ae; Byun, Eun Young; Song, Jae Young; Jung, Tae Sung; Lee, Byung Sang; Baik, Seung Chul; Cho, Myung Je; Youn, Hee Shang; Ko, Gyung Hyuck; Kim, Yong Sung; Park, Jong Hoon; Lee, Dae Sil; Yoo, Hyang Sook; Ghim, Sa Youl; Lee, Kwang Ho

Abstract

Helicobacter pylori is a causative agent of type B gastritis and plays a central role in the pathogenesis of gastroduodenal ulcer and gastric cancer. To elucidate the host-parasite relationship of the H. pylori infection on the basis of molecular biology, we tried to evaluate the genomic diversity of H. pylori. An ordered overlapping bacterial artificial chromosome (BAC) library of a Korean isolate, H, pylori 51 was constructed to set up a genomic map. A circular physical map was constructed by aligning ApaI, Notl and SfiI-digested chromosomal DNA. When the physical map of H. pylori 51 was compared to that of unrelated strain, H. pylori 26695, completely different restriction patterns were shown. Fifteen known genes were mapped on the chromosome of H. pylori 51 and the genetic map was compared with those of strain 26695 and J99, of which the entire genomic sequences were reported. There were some variability in the gene location as well as gene order among three strains. For further analysis on the genomic diversity of H. pylori, when comparing the genomic structure of 150 H. pylori Korean isolates with one another, genomic macrodiversity of H. pylori was characterized by several features: whether or not susceptible to restriction digestion of the chromsome, variation in chromosomal restriction fingerprint and/or high frequency of gene rearrangement. We also examined the extent of allelic variation in nucleotide or deduced amino acid sequences at the individual gene level. fucT, cagA and vacA were confirmed to carry regions of high variation in nucleotide sequence among strains. The plasticity zone and strain-specific genes of H. pylori 51 were analyzed and compared with the former two genomic sequences. It should be noted that the H. pylori 51-specific sequences were dispersed on the chromosome, not congregated in the plasticity zone unlike J99- or 26695-specific genes, suggesting the high frequency of gene rearrangement in H. pylori genome. The genomc of H. pylori 51 shows differences in the overall genomic organization, gene order, and even in the nucleotide sequences among the H. pylori strains, which are far greater than the differences reported on the genomic. diversity of H. pylori.