Fig. 4

Site-specific selection on β-lactamase inferred with experimentally informed models. The height of each letter above/below the black center line is proportional to the differential selection for/against that amino acid at that site relative to what is expected from the amino-acid preferences in Fig. 2. The overlay bar shows the evidence for diversifying selection at each site, which is manifested by strong evidence for a ratio ω _r of nonsynonymous to synonymous substitution rates that is higher (red) or lower (blue) than expected from the amino-acid preferences. The β-lactamase sequence is numbered using the Ambler scheme [82], meaning that residue numbers 239 and 253 are skipped. Comparable data for Gal4, NP, and HA are shown in Additional files 8, 9, and 10, respectively