Emergent gene order in a model of modular polyketide synthase system

نویسندگان

  • Ben Callahan
  • Mukund Thattai
  • Boris Shraiman
چکیده

Polyketides are widespread biologically active heteropolymers produced by ‘assembly line’-like multi-protein complexes formed by modular polyketide synthases (PKS). The nature of the polyketide product is encoded in the order of particular types of PKS proteins along the assembly line, suggesting that the diversity of polyketides derives from the combinatorial rearrangement of complexes formed by PKS modules. Remarkably, the order of PKS genes on the chromosome follows the order of PKS proteins along the assembly line: this fact is commonly referred to as ‘colinearity’. Here we propose a possible evolutionary origin for this colinearity and demonstrate the mechanism using a computational model of PKS evolution in a population. Assuming that polyketide biosynthesis is under a continuous selective pressure to evolve new products and that new polyketide pathways are formed through horizontal transfer and recombination of PKS encoding DNA, we demonstrate the existence of a broad range of parameters for which colinearity is expected to emerge. Although in our model colinearity confers no direct fitness advantage it is established and maintained through a ‘secondary’ selection mechanism, as a trait which increases the probability of formation of long functional PKS assemblies through recombination. Consequently, colinearity ‘hitch-hikes’ on the successful genotypes which periodically sweep through the continuously evolving population. In addition to the computer simulation of the simple model of PKS evolution we provide a mathematical framework describing the secondary selection mechanism, which generalizes beyond the context of PKSs.

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تاریخ انتشار 2008