Figure 9. Translocation of fitness landscapes in the sequence space of orthologous TIM barrels.

(a) Over evolutionary time, orthologous proteins adapt to changing environment for optimal fitness. Steps in sequence space select for protein stability and activity under their native conditions, all while retaining the TIM barrel fold and IGPS function. (b) Experimentally derived fitness landscapes mapped from point mutations represent single steps from WT sequence. Despite significant divergence of WT in sequence space, the fitness landscapes of IGPS orthologues remain correlated (dashed lines). Rather than traditional two-dimensional heatmaps, fitness values are displayed on a three-dimensional pinwheel, highlighting the wide range of possible fitness effects of a single sequence step. The profiles of the pinwheels are similar, indicating the correlation of fitness landscapes, even if WT sequences (centers of the wheels) are only ∼40% identical and widely separated. PCA demonstrates a correlation between experimental fitness landscapes and amino-acid preferences in evolved sequences.