Abstract
BACKGROUND: For last seven decades we remained convinced that the natural point mutations occur randomly in the genome of an organism. However, our whole genome sequence analyses show that for the gastric pathogen Helicobacter pylori, which causes peptic ulcer and gastric cancer, accumulations of point mutations in the genome are non-random and they contribute to its unidirectional evolution. Based on the oncoprotein CagA, the pathogen can be classified into Eastern (East Asian countries like China and Japan; high incidence of gastric cancer) and Western (Europe, Africa, South-West Asian countries like India; low incidence of gastric cancer) types. RESULTS: We have found a unique high-altitude Himalayan region, Sikkim (an Indian state bordering China, Nepal and Bhutan), where the evolving Eastern and Western H. pylori types co-exist and show the signs of genetic admixtures. Here, we present genomic evidence for more virulent Eastern-H. pylori getting converted to less virulent Western-H. pylori by accumulating non-random adaptive point mutations. CONCLUSION: The lesser virulence of the westernized H. pylori is beneficial since this pathogen typically remains colonized in the stomach for decades before causing terminal diseases like gastric cancer. Moreover, the mutation-driven westward evolution of H. pylori is a global phenomenon, which occurred in the geographical regions where people from Eastern and Western ethnicities met and cohabited. The identified evolution of virulent Eastern H. pylori strains to lesser virulent Western variants by accumulation of point mutations also provides insight into the pathogenic potentials of different H. pylori strains.