The Origins of Specificity in Polyketide Synthase Protein Interactions
Figure 6
Domain Shuffling and Domain Linkage
(A) ΔH is the fraction of amino acid differences between some pair of head domains; ΔT is the fraction of amino acid differences between some pair of tail domains. We compare the observed degree of similarity of two head domains (ΔH), with that of the two tail domains on the same proteins (ΔT) or the two tail domains that are their interaction partners (ΔT′). Each such comparison gives us a point in ΔH − ΔT space; by running over all possible pairs, we generate a family of points.
(B,C) Density plots of points in ΔH − ΔT space, with axes running from 0 (identical) to 1 (distinct). To generate these plots, a 2-D histogram was calculated by binning the data into a 10-by-10 grid, which was then smoothed by interpolation. The multimodal appearance of these plots is a manifestation of the underlying phylogenetic clusters.
(B) Density plot of ΔH versus ΔT, when the head and tail domains belong to the same protein. A priori, we expect two proteins descended from a common ancestor to show a uniform degree of sequence similarity across their entire length. Instead, we find that ΔH is largely uncorrelated with ΔT (cc = 0.13). That is, proteins with very similar head domains can have very diverged tail domains, and vice versa. This implies that proteins are not inherited in their entirety, but instead undergo frequent domain shuffling.
(C) Density plot of ΔH versus ΔT′, when the head and tail domains are interaction partners. In this case, ΔH and ΔT′ are highly correlated (cc = 0.67), implying that these two domains are evolutionarily linked. Remarkably, the interacting domain pair straddling two proteins, rather than the protein itself, constitutes the true unit of inheritance.