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

Yun-Juan Bao,Victoria A Ploplis,Francis J Castellino,B Jesse Shapiro,Shaun W Lee

doi:10.1038/srep36644

Yun-Juan Bao, Victoria A Ploplis + Show 3 more

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https://doi.org/10.1038/srep36644

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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.

Highlights

A systematic understanding and characterization of the genotype-phenotype correlations in infectious diseases remains a fundamental goal in physiological studies and clinical practices
We demonstrate a phenotypic differentiation of Group A Streptococcus pyogenes (GAS) strains associated with their clinical manifestations, i.e., skin infection and acute rheumatic fever
The associations are complex and in many cases are vague, especially in infectious diseases caused by bacterial pathogens, where phenotypic and genotypic heterogeneity make such systematic inferences difficult

Summary

Introduction

A systematic understanding and characterization of the genotype-phenotype correlations in infectious diseases remains a fundamental goal in physiological studies and clinical practices. Numerous population genomic studies on genome-wide single nucleotide polymorphisms (SNPs) have demonstrated the profound impact of genomic recombination on driving adaptation and accelerating evolution, such as resistance to antibiotics in Streptococcus pneumoniae[11], association with epidemic outbreaks in Legionella pneumophila[12], and serotype switching in Chlamydia trachomatis[13]. Genomic recombination has been shown to induce ecological differentiation via gene-specific selective sweeps in aquatic bacteria, such as Vibrio cyclitrophicus[14], Prochlorococcus[15], and Synechococcus[16], and in a soil bacteria population Mesorhizobium[17]. The wide range of infection-niche tropism and versatile adaptive capability of GAS have long been recognized to be largely associated with the highly plastic and transformable genome of this organism, as evidenced by frequent genomic recombination events observed in GAS genomes[25,26]. Neither evolutionary mechanisms of the adaptations, nor conclusive associations between the observed infection phenotypes and genotypic properties have been well defined

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