Structure and dynamics of the pan-genome of Streptococcus pneumoniaeand closely related species

Background: Streptococcus pneumoniaeis one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniaewere analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. Results: Despite evidence of extensive recombination, the S. pneumoniaephylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes - genes present in more than one strain but not in all strains - was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitiswas the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniaeincreased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniaestrains, but were also present in S. mitis, S. oralisand S. infantis, indicating that these genes are not sufficient to determine virulence. Conclusions: Genetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan-genome guarantees the species a quick and economical response to diverse environments.