FIG 5.

HMM PBP amino acid substitution sites and inferred signatures of evolutionary selection. (A to D) Schematics of the HMM PBPs are illustrated at the top of each panel. Shown are the functional domains and sites of parallel/convergent substitutions identified relative to the most prevalent variant. Substituted sites identified in two or more genetic lineages are indicated in black, and sites found in a single lineage but located within one of the conserved catalytic motifs of the transpeptidase domain are indicated in red. Sites identified as homoplasic are indicated by a plus sign in red. PBP2X substitutions linked with reduced susceptibility to one or more β-lactam antibiotics in vitro are highlighted in yellow. Graphed below each PBP schematic is the dN/dS ratio for each individual codon site determined with FUBAR. Sites identified as having a significant probability of evolving under positive selection by at least one test method (FUBAR, MEME, or SLAC) are numbered in red, and sites identified as significant by multiple methods are indicated by an asterisk. Indicated with tic marks below the graphs are significantly negatively selected sites in blue and significantly positively selected sites in red. To simplify the figures and because of their potential to distort evolutionary inferences, PBP genetic outlier recombinant alleles/variants were excluded from the generation of the schematics and the dN/dS determinations.