Gut and Liver, Vol. 6, No. 1, January 2012, pp. 21-28 review Evolutionary History of the Helicobacter pylori Genome: Implications for Gastric Carcinogenesis Pelayo Correa and M. Blanca Piazuelo Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA The genome of the bacterium Helicobacter pylori has evolved over the millennia since its migration out of Africa along with its human host approximately 60,000 years ago. Human mi- grations, after thousands of years of permanent settlement in those lands, resulted in seven prototypes of genetic popu- lations of H. pylori with distinct geographical distributions. In all continents, present day isolates of H. pylori have molecu- lar markers that reﬂect population migrations. The coloniza- tion of the Americas as well as the slave trade introduced European and African strains to the New World. The relation- ship between H. pylori genome and gastric cancer rates is linked to the presence of the cagA gene, but the knowledge on this subject is incomplete because other genes may be involved in certain populations. A new situation for Homo sapiens is the absence of H. pylori colonization in certain, mostly affluent, populations, apparently brought about by improved home sanitation and widespread use of antibiotics during the last decades. The disappearance of H. pylori from the human microbiota may be linked to emerging epidem- ics of esophageal adenocarcinoma, some allergic diseases such as asthma and some autoimmune disorders. (Gut Liver 2012;6:21-28) Key Words: Helicobacter pylori; Genome; Gastric carcinogen- esis INTRODUCTION Helicobacter pylori is a Gram-negative spiral bacterium that colonizes the gastric mucosa of more than half of the world population and is the main recognized cause of gastritis, peptic ulcers, gastric adenocarcinoma and some types of gastric lym- phoma.1-4 It has been estimated that human organisms consist of 1013 eukaryotic cells and 1014 microbial cells.5 H. pylori may be considered prominent member of the human microbiota and has accompanied constantly Homo sapiens in its complex mi- gration history.6 H. pylori is usually acquired during childhood and is believed to be transmitted within families. The bacterium is well adapted to survive in the gastric mucus for decades, and most infected persons remain asymptomatic. One of the characteristics of H. pylori is a great genetic diver- sity, and it is known that different strains may interact differ- ently with their human host influencing the clinical outcome. The extensive genomic diversity among H. pylori isolates results from a high mutation rate and a frequent exchange of genetic material during infections with multiple H. pylori strains.7-11 H. pylori strains from different geographic areas show clear phy- logeographic differentiation, and studies of the genetic variants serve as markers of human migrations. In addition, the world- wide geographic distribution of the different H. pylori popula- tions seems to correlate the clinical outcomes. This review ex- amines the role of H. pylori genomic variants in the biology and outcomes of the infection. CARCINOGENIC POTENTIAL Gastric cancer is the second leading cause of cancer-related death in the world.12 Based on epidemiologic evidence, the In- ternational Agency for Research on Cancer concluded in 1994 that the infection with H. pylori was a class I carcinogen for humans.13 It has been estimated that 5.5% of the total cases of cancer worldwide and more than 60% of gastric cancer cases are caused by this bacterial infection.14 Approximately one half of the gastric cancer cases occurs in East Asia, and the countries with the highest incidence rates are Korea, Mongolia, Japan, and China.15 Correspondence to: Pelayo Correa Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue 1030 MRB IV, Nashville, TN 37232-0252, USA Tel: +1-615-343-3958, Fax: +1-615-343-6229, E-mail: pelayo.correa@vanderbilt.edu Received on December 7, 2011. Accepted on December 26, 2011. pISSN 1976-2283 eISSN 2005-1212 http://dx.doi.org/10.5009/gnl.2012.6.1.21 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.