title: Using Whole Genome Analysis to Examine Recombination across Diverse Sequence Types of Staphylococcus aureus.
abstract: Staphylococcus aureus is an important clinical pathogen worldwide and understanding this organism's phylogeny and, in particular, the role of recombination, is important both to understand the overall spread of virulent lineages and to characterize outbreaks. To further elucidate the phylogeny of S. aureus, 35 diverse strains were sequenced using whole genome sequencing. In addition, 29 publicly available whole genome sequences were included to create a single nucleotide polymorphism (SNP)-based phylogenetic tree encompassing 11 distinct lineages. All strains of a particular sequence type fell into the same clade with clear groupings of the major clonal complexes of CC8, CC5, CC30, CC45 and CC1. Using a novel analysis method, we plotted the homoplasy density and SNP density across the whole genome and found evidence of recombination throughout the entire chromosome, but when we examined individual clonal lineages we found very little recombination. However, when we analyzed three branches of multiple lineages, we saw intermediate and differing levels of recombination between them. These data demonstrate that in S. aureus, recombination occurs across major lineages that subsequently expand in a clonal manner. Estimated mutation rates for the CC8 and CC5 lineages were different from each other. While the CC8 lineage rate was similar to previous studies, the CC5 lineage was 100-fold greater. Fifty known virulence genes were screened in all genomes in silico to determine their distribution across major clades. Thirty-three genes were present variably across clades, most of which were not constrained by ancestry, indicating horizontal gene transfer or gene loss.
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Driebe
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Sahl
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Chandler
authors.initials: C
authors.lastname: Roe
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Jolene R
authors.initials: JR
authors.lastname: Bowers
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Schupp
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Gillece
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: Kelley
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Lance B
authors.initials: LB
authors.lastname: Price
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America.
authors.forename: Talima R
authors.initials: TR
authors.lastname: Pearson
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America.
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Hepp
authors.affiliation: Thermo Fisher Scientific, South San Francisco, California, United States of America.
authors.forename: Pius M
authors.initials: PM
authors.lastname: Brzoska
authors.affiliation: Thermo Fisher Scientific, South San Francisco, California, United States of America.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Cummings
authors.affiliation: Thermo Fisher Scientific, South San Francisco, California, United States of America.
authors.forename: Manohar R
authors.initials: MR
authors.lastname: Furtado
authors.affiliation: Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Paal S
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Marc
authors.initials: M
authors.lastname: Stegger
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Engelthaler
authors.affiliation: Pathogen Genomics Division, The Translational Genomics Research Institute, Flagstaff, Arizona, United States of America; Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Keim
mesh_terms: D001499:Bayes Theorem; D016000:Cluster Analysis; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics*; D005838:Genotype; D009154:Mutation; D059645:Mutation Rate; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics