Population genetics and evolution of the pan-genome of Streptococcus pneumoniae

The genetic variability in bacterial species is much larger than in other kingdoms of life. The gene content between pairs of isolates can diverge by as much as 30% in species like Escherichia coli or Streptococcus pneumoniae. This unexpected finding led to the introduction of the concept of the pan-genome, the set of genes that can be found in a given bacterial species. The genome of any isolate is thus composed by a “core genome” shared by all strains and characteristic of the species, and a “dispensable genome” that accounts for many of the phenotypic differences between strains. The pan-genome is usually much larger than the genome of any single isolate and, given the ability of many bacteria to exchange genetic material with the environment, constitutes a reservoir that could enhance their ability to survive in a mutating environment. To understand the evolution of the pan-genome of an important pathogen and its interactions with the commensal microbial flora, we have analyzed the genomes of 44 strains of Streptococcus pneumoniae, one of the most important causes of microbial diseases in humans. Despite evidence of extensive homologous recombination, the S. pneumoniae phylogenetic tree reconstructed from polymorphisms in the core genome identified major groups of genetically related strains. 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 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 with related species sharing the same ecological niche was the main mechanism of evolution of S. pneumonia; and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome of S. pneumoniae increased logarithmically with the number of strains and linearly with the variability of the sample, suggesting that acquired genes accumulate proportionately to the age of clones.