A Systematic Computational Analysis of Biosynthetic Gene Cluster Evolution: Lessons for Engineering Biosynthesis
Figure 4
Qualitative model for the evolution of NRPS/PKS domains.
After modules are duplicated, they may get ‘trapped’ in a cycle in which small sequence divergences are counterbalanced by internal recombinations that drive concerted evolution. Through strong diversifying selection (or sufficient drift), domains may break out of this cycle towards domain sequences that are protected from concerted evolution by functional divergence and subsequent stabilizing selection on the new function, or by reduced internal recombination rates due to larger sequence differences between the domains. The abovementioned sequence divergence may occur through cumulative mutation or through recombination with other gene clusters (or other modules within the same gene cluster).