As readers of this blog know, I have proposed that introns have facilitated metazoan evolution. For example, after discussing alternative splicing, I noted:
It should now become clear to you why introns are so useful in a multicellular state and, conversely, why the cell design of a prokaryote could never have evolved something like a mouse. Introns impart extreme flexibility that would facilitate the emergence of different cell types under the constraint of the same genome.
Recent research has shown how one splicing network that is important in the development of the brain may have evolved. What’s interesting to me is not simply more data that supports my hypothesis about the role of introns in metazoan evolution, but that this gene network was pieced together prior to the emergence of the brain.
The article in PNAS focuses on the NOVA1 (neuro-oncological ventral antigen 1) protein, a splicing factor involved in the differential splicing of RNA. NOVA1 is present in all animal groups, in particular vertebrates, and regulates the production of messenger RNA with specific tissue-related functions. In the case of the central nervous system, messenger RNA encode basic proteins related to ion channels, neurotransmitter receptors, molecules involved in synapse formation, etc.
Previous studies had already confirmed the importance of NOVA1 in the architecture of the central nervous system. According to professor Jordi García-Fernàndez, “the study published in PNAS focuses principally on the generation of the NOVA1-regulated gene network and its development to full complexity in vertebrates, where NOVA1 specifically regulates tens or perhaps hundreds of genes in the central nervous system.”
The study describes the stepwise assembly of the NOVA1-regulated splicing network during the evolution of metazoans. In the first step of this process, the NOVA1 protein acquired the ability to perform vertebrate-like splicing modulation, at the time of the emergence of chordates. In the second step, expression of NOVA1 became restricted to the central nervous system, just before the emergence of vertebrates. The third step saw NOVA1 acquire new exons and targets during vertebrate evolution.
The study highlights that, despite containing a large number of similar genes, the human proteome is much larger and more complex than those of invertebrates. According to the conclusions presented, regulation of splicing factors and the creation of new exons are also key processes in the assembly of specific gene networks in complex systems — such as the human nervous system — via differential splicing.