Estimating recombinational parameters in Streptococcus pneumoniae from multilocus sequence typing data

Multilocus sequence typing (MLST) is a highly discriminatory molecular typi ng method that defines isolates of bacterial pathogens using the sequences of similar to 450-bp internal fragments of seven housekeeping genes. This t echnique has been applied to 575 isolates of Streptococcus pneumoniae and i dentifies a number of discrete clonal complexes. These clonal complexes are typically represented by a single group of isolates sharing identical alle les at all seven loci, plus single-locus variants that differ from this gro up at only one out of the seven loci. As MLST is highly discriminatory: the members of each clonal complex can be assumed to have a recent common ance stor, and the molecular events that give rise to the single-locus variants can be used to estimate the relative contributions of recombination and mut ation to clonal divergence. By comparing the sequences of the variant allel es within each clonal complex with the allele typically found within that c lonal complex, we estimate that recombination has generated new alleles at a frequency similar to 10-fold higher than mutation, and that a single nucl eotide site is similar to 50 times more likely to change through recombinat ion than mutation. We also demonstrate how to estimate the average length o f recombinational replacements from MLST data.