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Genomic Changes during Chronic Helicobacter pylori Infection

Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany,¹ Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany,² Berna Biotech, Ltd., Berne, Switzerland,³ Louisiana State University Medical Center, New Orleans, Louisiana,⁴ Division of Comparative Medicine, MIT, Cambridge, Massachusetts 02139,⁵ Mathematical Genetics Group, Department of Statistics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom⁶

Received 18 July 2005/ Accepted 6 October 2005

The gastric pathogen Helicobacter pylori shows tremendous genetic variability within human populations, both in gene content and at the sequence level. We investigated how this variability arises by comparing the genome content of 21 closely related pairs of isolates taken from the same patient at different time points. The comparisons were performed by hybridization with whole-genome DNA microarrays. All loci where microarrays indicated a genomic change were sequenced to confirm the events. The number of genomic changes was compared to the number of homologous replacement events without loss or gain of genes that we had previously determined by multilocus sequence analysis and mathematical modeling based on the sequence data. Our analysis showed that the great majority of genetic changes were due to homologous recombination, with 1/650 events leading to a net gain or loss of genes. These results suggest that adaptation of H. pylori to the host individual may principally occur through sequence changes rather than loss or gain of genes.

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