Emergence of the Synucleins

SIMPLE SUMMARY: Alpha-synuclein has been thoroughly analyzed due to its relevance to familial Parkinson’s disease and other synucleinopathies. In this study, I determine the origin of the synuclein genes in all vertebrates. Contrary to previous assumptions, these genes are not the result of individual gene duplications. They are ohnologs that emerged in several whole-genome duplications that occurred throughout vertebrate history. ABSTRACT: This study establishes the origin and evolutionary history of the synuclein genes. A combination of phylogenetic analyses of the synucleins from twenty-two model species, characterization of local synteny similarities among humans, sharks and lampreys, and statistical comparisons among lamprey and human chromosomes, provides conclusive evidence for the current diversity of synuclein genes arising from the whole-genome duplications (WGDs) that occurred in vertebrates. An ancestral synuclein gene was duplicated in a first WGD, predating the diversification of all living vertebrates. The two resulting genes are still present in agnathan vertebrates. The second WGD, specific to the gnathostome lineage, led to the emergence of the three classical synuclein genes, SNCA, SNCB and SNCG, which are present in all jawed vertebrate lineages. Additional WGDs have added new genes in both agnathans and gnathostomes, while some gene losses have occurred in particular species. The emergence of synucleins through WGDs prevented these genes from experiencing dosage effects, thus avoiding the potential detrimental effects associated with individual duplications of genes that encode proteins prone to aggregation. Additional insights into the structural and functional features of synucleins are gained through the analysis of the highly divergent synuclein proteins present in chondrichthyans and agnathans.