Abstract:
Bacillus anthracis, the causative agent of anthrax disease, is a worldwide threat to livestock, wildlife and public health. While
analyses of genetic data from across the globe have increased our understanding of this bacterium’s population genomic structure,
the influence of selective pressures on this successful pathogen is not well understood. In this study, we investigate the
effects of antimicrobial resistance, phage diversity, geography and isolation source in shaping population genomic structure.
We also identify a suite of candidate genes potentially under selection, driving patterns of diversity across 356 globally extant
B. anthracis genomes. We report ten antimicrobial resistance genes and 11 different prophage sequences, resulting in the
first large-scale
documentation of these genetic anomalies for this pathogen. Results of random forest classification suggest
genomic structure may be driven by a combination of antimicrobial resistance, geography and isolation source, specific to the
population cluster examined. We found strong evidence that a recombination event linked to a gene involved in protein synthesis
may be responsible for phenotypic differences between comparatively disparate populations. We also offer a list of genes
for further examination of B. anthracis evolution, based on high-impact
single nucleotide polymorphisms (SNPs) and clustered
mutations. The information presented here sheds new light on the factors driving genomic structure in this notorious pathogen
and may act as a road map for future studies aimed at understanding functional differences in terms of B. anthracis biogeography,
virulence and evolution.