Genome wide evolutionary analyses reveal serotype specific patterns of positive selection in selected Salmonella serotypes

Background: The bacterium Salmonella enterica includes a diversity of serotypes that cause disease in humans and different animal species. Some Salmonella serotypes show a broad host range, some are host restricted and exclusively associated with one particular host, and some are associated with one particular host species, but able to cause disease in other host species and are thus considered host adapted. Five Salmonella genome sequences, representing a broad host range serotype (Typhimurium), two host restricted serotypes (Typhi [two genomes] and Paratyphi) and one host adapted serotype (Choleraesuis) were used to identify core genome genes that show evidence for recombination and positive selection. Results: Overall, 3323 orthologous genes were identified in all 5 Salmonella genomes analyzed. Use of four different methods to assess homologous recombination identified 270 genes that showed evidence for recombination with at least one of these methods (false discovery rate [FDR] < 10%). After exclusion of genes with evidence for recombination, site and branch specific models identified 41 genes as showing evidence for positive selection (FDR < 20%), including a number of genes with confirmed or likely roles in virulence and ompC, a gene encoding an outer membrane protein, which has also been found to be under positive selection in other bacteria. A total of 8, 16, 7, and 5 genes showed evidence for positive selection in Choleraesuis, Typhi, Typhimurium, and Paratyphi branch analyses, respectively. Sequencing and evolutionary analyses of four genes in an additional 42 isolates representing 23 serotypes confirmed branch specific positive selection and recombination patterns. Conclusion: Our data show that, among the four serotypes analyzed, (i) less than 10% of Salmonella genes in the core genome show evidence for homologous recombination, (ii) a number of Salmonella genes are under positive selection, including genes that appear to contribute to virulence, and (iii) branch specific positive selection contributes to the evolution of host restricted Salmonella serotypes.