Ongoing purifying selection on intergenic spacers in group A streptococcus.

Bacterial intergenic spacers are non-coding genomic regions enriched with cis-regulatory elements for gene expression. A population genetics approach was used to investigate the evolutionary force shaping the genetic diversity of intergenic spacers among 13 genomes of group A streptococcus (GAS). Analysis of 590 genes and their linked 5' intergenic spacers showed reduced nucleotide diversity in spacers compared to synonymous nucleotide diversity in protein-coding regions, suggestive of past purifying selection on spacers. Certain spacers showed elevated nucleotide diversity indicative of past homologous recombination with divergent genotypes. In addition, analysis of the difference between mean nucleotide difference and number of segregating sites showed evidence of an excess of rare variants both at nonsynonymous sites in genes and at sites in spacers, which is evidence that there are numerous slightly deleterious variants in GAS populations with potential effects on both protein sequences and gene expression.