Progressive evolution offromsubsp.and adaption to equine hosts.

Abstract

subsp.causes the equine respiratory disease 'strangles', which is highly contagious, debilitating and costly to the equine industry.emerged from the ancestralsubsp.and continues to evolve and disseminate globally. Previous work has shown that there was a global population replacement around the beginning of the twentieth century, obscuring the early genetic events in this emergence. Here, we have used large-scale genomic analysis ofand its ancestorto identify evolutionary events, leading to the successful expansion of. One thousand two hundred one whole-genome sequences ofwere recovered from clinical samples or from data available in public databases. Seventy-four whole-genome sequences representative of the diversity ofwere used to compare the gene content and examine the evolutionary emergence of. A dated Bayesian phylogeny was constructed, and ancestral state reconstruction was used to determine the order and timing of gene gain and loss events between the different species and between differentlineages. Additionally, a newly developed framework was used to investigate the fitness of differentlineages. We identified a novellineage, comprising isolates from donkeys in Chinese farms, which diverged nearly 300 years ago, after the emergence offrom, but before the global sweep. Ancestral state reconstruction demonstrated that phage-encoded virulence factors,andwere acquired by the globalafter the divergence of the basal donkey lineage. We identified the equibactin locus in bothpopulations, but not, reinforcing its role as a keyvirulence mechanism involved in its initial emergence. Evidence of a further population sweep beginning in the early 2000s was detected in the UK. This clade now accounts for more than 80% of identified UK cases since 2016. Several sub-lineages demonstrated increased fitness, within which we identified the acquisition of a new, fifth prophage containing additional toxin genes. We definitively show that acquisition of the equibactin locus was a major determinant inbecoming an equid-exclusive pathogen, but that other virulence factors were fixed by the population sweep at the beginning of the twentieth century. Evidence of a secondary population sweep in the UK and acquisition of further advantageous genes implies thatis continuing to adapt, and therefore, continued investigations are required to determine further risks to the equine industry.