Fig. 2

An excerpt of the CBS variant effect (VE) maps and accordingly colorized structures of CBS. a A preview of the full map highlighting the region of the cut-out. A poster-sized version of the entire map can be found in Additional file 2: Figure S12. b A magnified cut-out of the VE maps for CBS covering amino acid 328–453: fitness landscape with low level (top) and high levels (center) of vitamin B₆ and the delta fitness (high − low vitamin B₆) landscape (bottom). In each plot, the first four rows indicate domain annotations, secondary structure, relative solvent accessibility, and burial in quaternary structure, respectively. The next subpanel summarizes the distribution of fitness scores at each amino acid position. The bottom subpanel shows fitness scores for each possible amino acid substitution and nonsense mutation. For high and low vitamin B₆ VE maps, a functional score of 0 (blue) corresponds to the median fitness of nonsense variants. A score of 1 (white) corresponds to the median fitness of synonymous variants. Yellow fields indicate the wildtype amino acid at each position. Gray fields indicate missing data. Diagonal lines indicate standard error, with crossed out fields marking variants for which standard error exceeded 1. For the delta fitness landscape (high − low vitamin B₆), substitutions were colored red if delta fitness score is positive and blue if negative. c, d Crystal structure of a CBS dimer with residues colored according to the median variant fitness with low vitamin B₆ (c) or the median delta fitness score (d). The CBS structure shown is based on PDB entry 4L3V [17]