Ancient origins of complex neuronal genes.

The largest animal genes, often spanning millions of base pairs, are known to be enriched for expression within nervous tissue and frequently mutated or misregulated in neurological disorders and diseases. In this work, we further characterize this group of large neuronal genes, finding that most are ancient, with origins predating the diversification of animals and in many cases the emergence of dedicated neuronal cell types. While these genes are highly constrained, with low dN/dS scores, they have also acquired substantial isoform diversity. These results suggest a highly conserved group of core protein structures have been maintained across the tree of life while being continuously and flexibly adapted through isoform diversification within nervous systems.