Introns on the Brain

I have not forgotten the Tetrahymena quiz, but I wanted to throw out one more juicy tidbt about introns first.  As I have suggested, introns may have facilitated the evolution of metazoan-like complexity and one possible mechanism is by making alternative splicing possible.  Recall that alternative splicing enables a single genome to spawn immensely diverse set of gene products, something that would come in very handy when it comes to spawning multiple cell types.  But we might get even more radical, as introns, along with alternative splicing may very well have facilitated the emergence of the brain.  In fact, we could even make a reasonable case that without introns, there would be no brains to discover introns.  Consider just three examples:

The evolution of alternative splicing in eukaryotes greatly expanded the number of functionally distinct proteins that could be produced from a finite gene pool. Extensive in the brains of higher organisms, alternative splicing might be the primary mechanism for generating the spectrum of protein activities that support complex brain functions. Alternative splicing is controlled at the level of individual neurons to custom design proteins for optimal performance. The expression profiles of splice isoforms are modified during development and as neuronal activity changes. Alternative splicing can lead to incremental, long lasting changes in ion channel and receptor activities, independent of changes in gene transcription. Recent studies of tissue-specific splicing factors are revealing how coordinated alterations in alternative splicing of RNA transcripts control synaptic function.

Diane Lipscombe. 2005. Neuronal proteins custom designed by alternative splicing. Current Opinion in Neurobiology 15:358–363

and

Alternative splicing events greatly expand the diversity of the genetic messages and corresponding proteins produced by genes in vertebrate cells and this process partially accounts for the evolution of remarkable complexity in organs such as the mammalian brain. Calarco, recipient of a prestigious Alexander Graham Bell Studentship, together with colleagues in the Blencowe lab, identified nSR100 using computational and experimental methods and then determined its role in the control of alternative splicing in the brain. These studies revealed that nSR100 regulates splicing events in genes that help form neurons.

[…]

Calarco added that the findings present a new avenue of investigation for researchers. “The study provides intriguing insight into how the evolution of a single protein has contributed to the expansion of brain complexity in vertebrates – including humans.

Here

and

RNA splicing is the process by which the initial RNA copy of a gene, known as pre-mRNA, is pieced together to produce a mature mRNA that codes for cellular proteins. In alternative splicing, different pieces of this pre-mRNA, called exons, are stitched together to produce different mRNAs, and thus different proteins. The exon can be spliced in or out in a binary, computer-like fashion. By regulating alternative splicing cells can produce a wide variety of proteins from a finite number of genes. This capacity is believed to be critical to the complex workings of human cells such as those found in the neurons of the brain.

“Given that the complexity of the brain is orders and orders of magnitude more complex than the number of genes we have, one of the intriguing things about alternative splicing is that a relatively small number of regulatory splicing factors acting in concert on a single transcript can potentially generate a large number of different protein variants,” says Darnell.

Here

Something to flesh out in the future, eh?

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