PT - JOURNAL ARTICLE AU - Matt Bawn AU - Gaetan Thilliez AU - Mark Kirkwood AU - Nicole Wheeler AU - Liljana Petrovska AU - Timothy J. Dallman AU - Neil Hall AU - Robert A. Kingsley TI - Evolution of <em>Salmonella enterica</em> serotype Typhimurium driven by anthropogenic selection and niche adaptation AID - 10.1101/804674 DP - 2019 Jan 01 TA - bioRxiv PG - 804674 4099 - http://biorxiv.org/content/early/2019/10/21/804674.short 4100 - http://biorxiv.org/content/early/2019/10/21/804674.full AB - Salmonella enterica serotype Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and disseminated disease worldwide, and a model organism for host pathogen interactions. Genotypic variation of S. Typhimurium results in strains with diverse host range, pathogenicity and risk to food safety. A robust fully parsimonious phylogenetic tree constructed from recombination purged variation in the whole genome sequence of 131 diverse strains of S. Typhimurium revealed population structure composed of two high order clades (α and β) and multiple subclades on extended internal branches, that exhibited distinct signatures of host adaptation and anthropogenic selection. Clade α contained a number of subclades composed of strains from well characterized epidemics in domesticated animals, while clade β predominantly contained subclades associated with wild avian species, with the notable exception of a subclade containing the DT204/49 complex. The contrasting epidemiology of α and β strains was reflected in distinct distribution of antimicrobial resistance (AMR) genes, accumulation of hypothetically disrupted coding sequences (HDCS), and signatures of functional diversification associated with invasiveness of host adapted serotypes. Gene flux was predominantly driven by acquisition, loss or recombination of prophage, awhile acquisition of large genetic islands (SGI-1 and 4) was restricted to two recent pandemic clones (DT104 and monophasic S. Typhimurium ST34) in clade α. Together, our data are consistent with the view that a broad host range common ancestor of S. Typhimurium diversified with clade α lineages remained largely associated with multiple domesticated animal species, while clade β spawned multiple lineages that underwent diversifying selection associated with adaptation to various niches, predominantly in wild avian species.