Heterogeneity in the frequency and characteristics of homologous recombination in pneumococcal evolution.
The bacterium Streptococcus pneumoniae (pneumococcus) is one of the most important human bacterial pathogens, and a leading cause of morbidity and mortality worldwide. The pneumococcus is also known for undergoing extensive homologous recombination via transformation with exogenous DNA. It has been shown that recombination has a major impact on the evolution of the pathogen, including acquisition of antibiotic resistance and serotype-switching. Nevertheless, the mechanism and the rates of recombination in an epidemiological context remain poorly understood. Here, we proposed several mathematical models to describe the rate and size of recombination in the evolutionary history of two very distinct pneumococcal lineages, PMEN1 and CC180. We found that, in both lineages, the process of homologous recombination was best described by a heterogeneous model of recombination with single, short, frequent replacements, which we call micro-recombinations, and rarer, multi-fragment, saltational replacements, which we call macro-recombinations. Macro-recombination was associated with major phenotypic changes, including serotype-switching events, and thus was a major driver of the diversification of the pathogen. We critically evaluate biological and epidemiological processes that could give rise to the micro-recombination and macro-recombination processes.
Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, London, United Kingdom.
Rafal
R
Mostowy
Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, London, United Kingdom; Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, United States of America; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Nicholas J
NJ
Croucher
Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
William P
WP
Hanage
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Simon R
SR
Harris
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
Stephen
S
Bentley
Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, London, United Kingdom.
Christophe
C
Fraser
D004352:Drug Resistance, Microbial / Q000235:genetics; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D018740:Genetic Heterogeneity; D008957:Models, Genetic; D011995:Recombination, Genetic; D013296:Streptococcus pneumoniae / Q000235:genetics*