The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement.
Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. AlthoughBordetella pertussisis well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257B. pertussisisolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with >240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution inB. pertussisis not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology.IMPORTANCEWhooping cough, primarily caused byBordetella pertussis, has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome ofB. pertussisincludes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology.
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA mweigand@cdc.gov.
Michael R
http://orcid.org/0000-0002-7278-0160
MR
Weigand
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Yanhui
Y
Peng
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Vladimir
V
Loparev
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Dhwani
D
Batra
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Katherine E
KE
Bowden
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Mark
M
Burroughs
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Pamela K
PK
Cassiday
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Jamie K
JK
Davis
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Taccara
T
Johnson
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Phalasy
P
Juieng
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Kristen
K
Knipe
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Marsenia H
MH
Mathis
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Andrea M
AM
Pruitt
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Lori
L
Rowe
Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Mili
M
Sheth
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
M Lucia
ML
Tondella
Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Margaret M
MM
Williams
D001886:Bordetella pertussis; D002876:Chromosomes, Bacterial / Q000235:genetics*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D023061:Gene Order / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D008040:Genetic Linkage; D014644:Genetic Variation / Q000235:genetics; D016680:Genome, Bacterial; D010802:Phylogeny
Bordetella pertussis; evolution; genomics; pertussis; rearrangement; whooping cough