Yamaoka et al. postulated that the geographical differences that are observed in the incidence of gastric cancer could be explained by different H. pylori strains (with regard to the distribution of cagA and vacA genotype) [13]. CagA is injected in the host cell through the Type IV secretion system (T4SS) which is coded by Cag Pathogenicity
Island (cagPAI) genes. These genes are also involved in horizontal gene transfer (HGT). Genes integrated into the H. pylori genome via HGT may have originated from either other bacteria or eukaryotic cells [14]. Olbermann et al.[15] analyzed the mTOR activation selection pressure for cagPAI genes and found HMPL-504 order that one-third of the genes were under positive selection. Most of the genes under positive selection, including the cagA gene, PLX3397 cost code for surface-exposed proteins. In positive selection, mutations increase fitness and, thus, new alleles increase in frequency in the population. In neutral (or nearly neutral) selection, mutations have no drastic effect on fitness and increase or decrease in frequency by chance. When fitness decreases due to deleterious mutations, new alleles are removed through purifying selection (i.e. virD4 and virB11 found in T4SS) [15]. Several authors have proposed that the pldA gene (coding for outer membrane phospholipase A, OMPLA) is important for the ability of the bacterium to colonize
the human gastric ventricle [16, 17]. Tannæs et al.[18] characterized a classical phase-variation in this gene due to DNA slippage in a homopolymeric tract that results in either a complete (pldAON) or truncated protein (pldAOFF). The homopolymeric tract was found in all of the clinical isolates of H. pylori sequenced by Tannæs et al.[18]. The conservation of the homopolymeric tract in this gene through phylogenesis underlines the importance of the gene product and maintenance of the phase variation for this bacterium. This study investigated the evolution of the pldA Molecular motor gene in H. pylori.
In silico sequence analysis was used to determine whether the bacteria were in the process of preserving, optimizing, or perhaps even rejecting the pldA gene. Sequences of pldA were compared by both identity and phylogenetic analysis to a reference set of HK genes from a large number of isolates sequenced by Falush et al.[11]. Horizontal gene transfer prediction was carried out via both intra- and inter-species phylogenetic analysis using related taxa and the estimation of both codon bias and GC content in H. pylori isolates. Results CagA EPIYA genotyping All of the 20 Korean sequences had an East Asian cagA ABD genotype. Nearly all of the 50 isolates analyzed from Norway had Western cagA genotypes, with the following distribution: 66% ABC, 12% ABCC, 12% AB, 4% ABCCC, and 2% AC. The two isolates collected from patients with East Asian origins displayed a cagA ABD genotype (4%).