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3044610 
Journal Article 
The distant siblings - a phylogenomic roadmap illuminates the origins of extant diversity in fungal aromatic polyketide biosynthesis 
Koczyk, G; Dawidziuk, A; Popiel, D 
2015 
English 
In recent years, the influx of newly sequenced fungal genomes has enabled sampling of secondary metabolite biosynthesis on an unprecedented scale. However, explanations of extant diversity which take into account both large-scale phylogeny reconstructions and knowledge gained from multiple genome projects are still lacking.We analysed the evolutionary sources of genetic diversity in aromatic polyketide biosynthesis in over a hundred model fungal genomes. By reconciling the history of over four hundred non-reducing polyketide synthases with corresponding species history, we demonstrate that extant fungal NR-PKSs are clades of distant siblings, originating from a burst of duplications in early Pezizomycotina and thinned by extensive losses.The capability of higher fungi to biosynthesise the simplest precursor molecule (orsellinic acid) is highlighted as an ancestral trait underlying biosynthesis of aromatic compounds. This base activity was modified during early evolution of filamentous fungi, towards divergent reaction schemes associated with biosynthesis of e.g. aflatoxins and fusarubins (C4-C9 cyclisation) or various anthraquinone derivatives (C6-C11 cyclisation). The functional plasticity is further shown to have been supplemented by modularisation of domain architecture into discrete pieces (conserved splice junctions within product template domain), as well as tight linkage of key accessory enzyme families and divergence in employed transcriptional factors.While the majority of discord between species and gene history is explained by ancient duplications, this landscape has been altered by more recent duplications, as well as multiple Horizontal Gene Transfers. The 25 detected transfers include previously undescribed events leading to emergence of e.g. fusarubin biosynthesis in Fusarium genus.Both the underlying data and the results of present analysis (including alternative scenarios revealed by sampling multiple reconciliation optima) are maintained as a freely available web-based resource: http://cropnet.pl/metasites/sekmet/nrpks_2014.