A Systematic Computational Analysis of Biosynthetic Gene Cluster Evolution: Lessons for Engineering Biosynthesis
Figure 5
Diverse and distinct modes of evolution for PKS and NRPS BGCs.
a, Scatter plot showing the first two principal components resulting from a PCA analysis of different evolutionary characteristics of BGCs encoding different classes of NRPs and PKs. The first two principal components describe 63% of the variance. BGCs encoding members of the same family (e.g., lipopeptides, glycopeptides or macrolides) tend to cluster together, suggesting that their family members evolve in similar ways, while different families cluster apart from each other, suggesting distinct modes of evolution. Colors indicate distinct classes of BGCs. b, Scatter plot showing two features of BGCs – internal similarity index and vertical evolution index – that, of the 25 measured features, underlie most of the variation. The internal similarity index indicates how similar domains in a BGC are to other domains within the same BGC. The vertical evolution index indicates how closely related a BGC is to the BGCs harboring the closest relatives of its constituent domains (see Methods for more details). Colors indicate distinct classes of BGCs, as in panel a. c–f, Domain architecture plots of PKSs and NRPSs show distinct modes of evolution: c, Internal duplication with concerted evolution; d, N-terminal additions by module duplication and recombination; e, domain swapping with other BGCs; and f, mixed evolution. Geometric shapes indicate domain types (see legend); domain colors indicate the internal homology p-value of each domain to its closest relative within the same gene cluster, within the total distribution of all similarities between domains of the same type in the entire data set: hence, domains colored red are most similar, while domains colored blue are most dissimilar.