Abstract
MotivationFunctional prediction of paralogs is challenging in bioinformatics because of rapid functional diversification after gene duplication events combined with parallel acquisitions of similar functions by different paralogs. Plant type III polyketide synthases (PKSs), producing various secondary metabolites, represent a paralogous family that has undergone gene duplication and functional alteration. Currently, there is no computational method available for the functional prediction of type III PKSs.ResultsWe developed a plant type III PKS reaction predictor, pPAP, based on the recently proposed classification of type III PKSs. pPAP combines two kinds of similarity measures: one calculated by profile hidden Markov models (pHMMs) built from functionally and structurally important partial sequence regions, and the other based on mutual information between residue positions. pPAP targets PKSs acting on ring-type starter substrates, and classifies their functions into four reaction types. The pHMM approach discriminated two reaction types with high accuracy (97.5%, 39/40), but its accuracy decreased when discriminating three reaction types (87.8%, 43/49). When combined with a correlation-based approach, all 49 PKSs were correctly discriminated, and pPAP was still highly accurate (91.4%, 64/70) even after adding other reaction types. These results suggest pPAP, which is based on linear discriminant analyses of similarity measures, is effective for plant type III PKS function prediction.Availability and ImplementationpPAP is freely available at ftp://ftp.genome.jp/pub/tools/ppap/Supplementary information Supplementary data are available at Bioinformatics online.
Highlights
Gene duplication followed by mutations produces paralogous genes with related functions
We extracted sequences corresponding to Areas 1–4 in known plant type III polyketide synthases (PKSs) of the R-4-A, R-4-C and R-2-X types from their Multiple sequence alignment (MSA) using M. sativa CHS2 as a reference (Fig. 2A and B)
We used the Areas corresponding to structural differences between R-4-A and R-4-C types for constructing profile hidden Markov models (pHMMs)
Summary
Gene duplication followed by mutations produces paralogous genes with related functions. Plant type III polyketide synthases (PKSs) are one such paralogous family and produce polyketides (PKs), a group of secondary metabolites exhibiting large diversity in their chemical structures and physiological functions (Abe and Morita, 2010). PKSs are classified into three types (I, II and III) based on their domain structure and subunit composition (Austin and Noel, 2003). Type III PKSs accept various acyl-CoAs called starter substrates and catalyze a cycle of decarboxylative condensations between the starter substrate and malonyl-CoA extender units to produce a polyketide intermediate. Despite the simple structure of type III PKSs, variations in starter substrates, numbers of extensions (and rare extender substrates) and reaction mechanisms of intramolecular cyclization generate a large diversity of PK products (Fig. 1). Type I and II PKSs have been classified based on their domain
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