title: Extraordinary conservation, gene loss, and positive selection in the evolution of an ancient neurotoxin.
abstract: The recent determination of the genetic basis for the biosynthesis of the neurotoxin, saxitoxin, produced by cyanobacteria, has revealed a highly complex sequence of reactions, involving over 30 biosynthetic steps encoded by up to 26 genes clustered at one genomic locus, sxt. Insights into evolutionary-ecological processes have been found through the study of such secondary metabolites because they consist of a measurable phenotype with clear ecological consequences, synthesized by known genes in a small number of species. However, the processes involved in and timing of the divergence of prokaryotic secondary metabolites have been difficult to determine due to their antiquity and the possible frequency of horizontal gene transfer and homologous recombination. Through analyses of gene synteny, phylogenies of individual genes, and analyses of recombination and selection, we identified the evolutionary processes of this cluster in five species of cyanobacteria. Here, we provide evidence that the sxt cluster appears to have been largely vertically inherited and was therefore likely present early in the divergence of the Nostocales, at least 2,100 Ma, the earliest reliably dated appearance of a secondary metabolite. The sxt cluster has been extraordinarily conserved through stabilizing selection. Genes have been lost and rearranged, have undergone intra- and interspecific recombination, and have been subject to duplication followed by positive selection along the duplicated lineage, with likely consequences for the toxin analogues produced. Several hypotheses exist as to the ecophysiological role of saxitoxin: as a method of chemical defense, cellular nitrogen storage, DNA metabolism, or chemical signaling. The antiquity of this gene cluster indicates that potassium channels, not sodium channels, may have been the original targets of this compound. The extraordinary conservation of the machinery for saxitoxin synthesis, under radically changing environmental conditions, shows that it has continued to play an important adaptive role in some cyanobacteria.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, New South Wales, Australia.
authors.forename: Shauna A
authors.initials: SA
authors.lastname: Murray
authors.forename: Troco K
authors.initials: TK
authors.lastname: Mihali
authors.forename: Brett A
authors.initials: BA
authors.lastname: Neilan
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics*; D000458:Cyanobacteria / Q000145:classification / Q000235:genetics; D019143:Evolution, Molecular; D017353:Gene Deletion; D020440:Gene Duplication; D005798:Genes, Bacterial / Q000502:physiology; D006801:Humans; D005810:Multigene Family; D009498:Neurotoxins / Q000096:biosynthesis / Q000145:classification / Q000235:genetics* / Q000506:poisoning; D010802:Phylogeny; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000506:poisoning; D015221:Potassium Channels / Q000378:metabolism; D011995:Recombination, Genetic; D012530:Saxitoxin / Q000096:biosynthesis / Q000145:classification / Q000235:genetics* / Q000506:poisoning; D012641:Selection, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D026801:Synteny / Q000235:genetics
chemical_list: D009498:Neurotoxins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012530:Saxitoxin