Evolutionary History of hrgA , Which Replaces the Restriction Gene hpy IIIR in the hpy III Locus of Helicobacter pylori

Abstract

ABSTRACT A recently identified Helicobacter pylori gene, hrgA , was previously reported to be present in 70 (33%) of 208 strains examined (T. Ando, T. M. Wassenaar, R. M. Peek, R. A. Aras, A. I. Tschumi, L.-J. Van Doorn, K. Kusugami, and M. J. Blaser, Cancer Res. 62: 2385-2389, 2002). Sequence analysis of nine such strains indicated that in each strain hrgA replaced hpy IIIR, which encodes a restriction endonuclease and which, together with the gene for its cognate methyltransferase, constitutes the hpy III locus. As a consequence of either the hrgA insertion or independent mutations, hpy IIIM function was lost in 11 (5%) of the 208 strains examined, rendering chromosomal DNA sensitive to Mbo I digestion. The evolutionary history of the locus containing either hpy III or hrgA was reconstructed. By homologous recombination involving flanking sequences, hrgA and hpy IIIR can replace one another in the hpy III locus, and there is simultaneous replacement of several flanking genes. These findings, combined with the hpy IM /iceA2 locus discovered previously, suggest that the two most strongly conserved methylase genes of H. pylori , hpy IIIM and hpy IM, are both preceded by alternative genes that compete for presence at their loci.