Conserved Patterns of Symmetric Inversion in the Genome Evolution of Bordetella Respiratory Pathogens

Abstract

Whooping cough (pertussis), primarily caused by Bordetella pertussis, has resurged in the United States, and circulating strains exhibit considerable chromosome structural fluidity in the form of rearrangement and deletion. The genus Bordetella includes additional pathogenic species infecting various animals, some even causing pertussis-like respiratory disease in humans; however, investigation of their genome evolution has been limited. We studied chromosome structure in complete genome sequences from 167 Bordetella species isolates, as well as 469 B. pertussis isolates, to gain a generalized understanding of rearrangement patterns among these related pathogens. Observed changes in gene order primarily resulted from large inversions and were only detected in species with genomes harboring multicopy insertion sequence (IS) elements, most notably B. holmesii and B. parapertussis. While genomes of B. pertussis contain >240 copies of IS481, IS elements appear less numerous in other species and yield less chromosome structural diversity through rearrangement. These data were further used to predict all possible rearrangements between IS element copies present in Bordetella genomes, revealing that only a subset is observed among circulating strains. Therefore, while it appears that rearrangement occurs less frequently in other species than in B. pertussis, these clinically relevant respiratory pathogens likely experience similar mutation of gene order. The resulting chromosome structural fluidity presents both challenges and opportunity for the study of Bordetella respiratory pathogens. IMPORTANCE Bordetella pertussis is the primary agent of whooping cough (pertussis). The Bordetella genus includes additional pathogens of animals and humans, including some that cause pertussis-like respiratory illness. The chromosome of B. pertussis has previously been shown to exhibit considerable structural rearrangement, but insufficient data have prevented comparable investigation in related species. In this study, we analyze chromosome structure variation in several Bordetella species to gain a generalized understanding of rearrangement patterns in this genus. Just as in B. pertussis, we observed inversions in other species that likely result from common mutational processes. We used these data to further predict additional, unobserved inversions, suggesting that specific genome structures may be preferred in each species.

Duplications drive diversity inBordetella pertussison an underestimated scale

“…The unusually high number of insertion sequences within the B. pertussis genome, and their relatively even distribution, likely facilitates the genome-wide distribution of structural variants. Indeed, genomes of related species B. parapertussis and B. holmesii each harbour fewer IS elements and thus exhibit fewer rearrangements (Weigand et al 2019) and very rare CNVs (M.R. Weigand, unpublished).…”

Whoop! There it is: The surprising resurgence of pertussis

“…Recent whole genome sequencing and chromosomal analyses of circulating Bp (cBp) strains changed the prevailing view of Bp as a monomorphic pathogen with small genetic changes and SNPs. Instead, cBp strains represent a dynamic population whose genomes exhibit extensive structural rearrangements including large inversions, duplications, and deletions [3,4]. Nonetheless, comparative genomics alone cannot sufficiently explain pertussis resurgence.…”

Bordetella Type III Secretion Injectosome and Effector Proteins

“…B. pertussis Tohama I ~ 4.1 Mbp, B. parapertussis HU 12822 ~ 4.8 Mbp, B. parapertussis OV Bpp5 ~ 4.9 Mbp, B. bronchiseptica RB50 ~ 5.3 Mbp). These genomic rearrangements were apparently mediated by the acquisition and expansion of insertion sequence elements (ISEs) and recombination between their copies (Parkhill et al, 2003 ; Preston et al, 2004 ; Weigand et al, 2019 ). Interestingly, host adaptation and speciation of classical Bordetella species likely was a consequence of loss of function, rather than a gain of function.…”