Phenotypic differentiation of Streptococcus pyogenes populations is induced by recombination-driven gene-specific sweeps

Abstract

Genomic recombination plays an important role in driving adaptive evolution and population differentiation in bacteria. However, controversy exists as to the effects of recombination on population diversity and differentiation, i.e., recombination is frequent enough to sweep through the population at selected gene loci (gene-specific sweeps), or the recombination rate is low without interfering genome-wide selective sweeps. Observations supporting either view are sparse. Pathogenic bacteria causing infectious diseases are promising candidates to provide observations of recombination. However, phenotype-associated differentiations are usually vague among them due to diverse disease manifestations. Here we report a population genomic study of the group A Streptococcus pyogenes (GAS), a human pathogen with highly recombining genomes. By employing a genome-wide association study on single nucleotide polymorphisms (SNPs), we demonstrate a phenotypic differentiation of GAS, represented by separate clustering of two sublineages associated with niche-specific infections, i.e., skin infection and pharyngitis-induced acute rheumatic fever. By quantifying SNPs associated with the differentiation in a statistical and phylogenetic context, we propose that the phenotype-associated differentiation arose through recombination-driven gene-specific sweeps, rather than genome-wide sweeps. Our work provides a novel paradigm of phenotype-associated differentiation induced by gene-specific sweeps in a human pathogen and has implications for understanding of driving forces of bacterial evolution.

Adaptation in a Fibronectin Binding Autolysin of Staphylococcus saprophyticus

“…The aas _2206A>C mutation is among the genetic variants that differentiate bacteria associated with human-pathogenic niches from those associated with other niches (i.e., it is an F ST outlier). SNPs associated with specific clinical phenotypes in the pathogen Streptococcus pyogenes were described recently ( 55 ), which is consistent with our finding that clinical phenotypes can represent distinct niche spaces preferentially occupied by subpopulations of bacteria. There is also precedent for a single nucleotide polymorphism to affect host tropism of bacteria ( 56 ).…”

Comparative pathogenomic characterization of a non-invasive serotype M71 strain Streptococcus pyogenes NS53 reveals incongruent phenotypic implications from distinct genotypic markers

“…Alternatively, it is possible that selection mechanisms acting on NS53 have been against the polymorphisms common to other skin tropic isolates. Similar incongruences were also observed for M3 and M14 GAS isolates (Bao et al 2016b). These observations reiterate the multifaceted correlation between genotypes and phenotypes of GAS, and single genetic markers may not be sufficient for precise prediction of the phenotypes of individual strains.…”

“…Our previous study, based on genomewide SNPs, demonstrated an association between genetic variations and tissue-specific diseases in GAS (Bao et al 2016b). …”

“…identified 895 SNPs and 221 non-synonymous SNPs significantly associated with skin infection using a genome-wide association study (Bao et al 2016b). Among them, only 206 (23.0%) and 41 (18.6%) were found in NS53, respectively.…”

Gene-centric intra- and inter-clade recombination in a context ofEsche-richia colisubpopulations

“…The assessment of mobility for each single gene indicates that high recombination rate does not have impact on genes with critical adaptive functions as well as GOF and primary metabolic portfolios they built over long evolutionary time scale when genes or their alleles are constantly shuffled by the high-rate recombination until reach assortive locations and fixed by nature selection in a manner of cut-and-try. Besides niche adaptation, nature also selects for higher genetic compatibility among metabolic pathways, genes, and even alleles, such as the CAVs in our case, because conflicts among these components may undermine the competence of host strains in constant competitions with adjacent sister strains (39). Thus GOF and primary metabolic portfolios and their related genes may be resistant to recombination that results in allele substitution(40) and location rearrangement(41) because phylogenies with reduced integrated fitness may be eliminated by nature selections.…”