Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus

Richard G Everitt,Ruth R Miller,Daniel J Wilson,Rory Bowden,Hanna Larner-Svensson,Elizabeth M Batty,Antonina Votintseva,Tim E A Peto,Rowena Fung,Derrick W Crook,Bernadette C Young,Heather Godwin,Jane Charlesworth,Adam Auton,Xavier Didelot,Camilla L C Ip,Tanya Golubchik,Kyle Knox,A Sarah Walker

doi:10.1038/ncomms4956

Abstract

Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus, is incompletely understood. Here we reveal widespread homologous recombination in S. aureus at the species level, in contrast to its near-complete absence between closely related strains. We discover a patchwork of hotspots and coldspots at fine scales falling against a backdrop of broad-scale trends in rate variation. Over megabases, homoplasy rates fluctuate 1.9-fold, peaking towards the origin-of-replication. Over kilobases, we find core recombination hotspots of up to 2.5-fold enrichment situated near fault lines in the genome associated with mobile elements. The strongest hotspots include regions flanking conjugative transposon ICE6013, the staphylococcal cassette chromosome (SCC) and genomic island νSaα. Mobile element-driven core genome transfer represents an opportunity for adaptation and challenges our understanding of the recombination landscape in predominantly clonal pathogens, with important implications for genotype–phenotype mapping.

Highlights

Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus, is incompletely understood
In the absence of homologous recombination mediated by horizontal gene transfer (HGT), adaptation in the core genome would be limited by the supply of new mutations and clonal interference[7]
We discover a patchwork of hotspots and coldspots in the core genome driven by proximity to mobile elements against a backdrop of broad-scale trends in recombination rate variation that peak towards the origin-of-replication

Summary

Introduction

Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus, is incompletely understood. We find core recombination hotspots of up to 2.5-fold enrichment situated near fault lines in the genome associated with mobile elements. ICE6013, the staphylococcal cassette chromosome (SCC) and genomic island nSaa. Mobile element-driven core genome transfer represents an opportunity for adaptation and challenges our understanding of the recombination landscape in predominantly clonal pathogens, with important implications for genotype–phenotype mapping. In the absence of homologous recombination mediated by HGT, adaptation in the core genome would be limited by the supply of new mutations and clonal interference[7]. The presence of CGT in apparently untransformable bacteria, among them major pathogens including Staphylococcus aureus, remains a paradox, and the underlying mechanisms obscure[10,11,12]

Methods

Results

Conclusion