Naturally occurring horizontal gene transfer and homologous recombination in Mycobacterium

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Abstract
Acquisition of genetic information through horizontal gene transfer (HGT) is an important evolutionary process by which micro-organisms gain novel phenotypic characteristics. In pathogenic bacteria, for example, it facilitates maintenance and enhancement of virulence and spread of drug resistance. In the genusMycobacterium, to which several primary human pathogens belong, HGT has not been clearly demonstrated. The few existing reports suggesting this process are based on circumstantial evidence of similarity of sequences found in distantly related species. Here, direct evidence of HGT between strains ofMycobacterium aviumrepresenting two different serotypes is presented. Conflicting evolutionary histories of genes encoding elements of the glycopeptidolipid (GPL) biosynthesis pathway led to an analysis of the GPL cluster genomic sequences from fourMycobacterium aviumstrains. The sequence ofM. aviumstrain 2151 appeared to be a mosaic consisting of three regions having alternating identities to eitherM. aviumstrains 724 or 104. Maximum-likelihood estimation of two breakpoints allowed a ∼4100 bp region horizontally transferred into the strain 2151 genome to be pinpointed with confidence. The maintenance of sequence continuity at both breakpoints and the lack of insertional elements at these sites strongly suggest that the integration of foreign DNA occurred by homologous recombination. To our knowledge, this is the first report to demonstrate naturally occurring homologous recombination inMycobacterium. This previously undiscovered mechanism of genetic exchange may have major implications for the understanding ofMycobacteriumpathogenesis.

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