Tag Archives: rapid protein evolution using microexons

MicroExons

MicroExons have been known for a long time.  They are hard to find using the usual software tools because they are short, coding for just 1 (!) to 9 amino acids (3 – 27 nucleotides).  The neurologist is interested in them, because they are enriched in neurons.

 

The evolutionist is interested in them because they are found on the surfaces of proteins, so that adding their amino acids potentially modifies protein protein interactions (example later) since these are largely determined at the protein surface.  The typical protein interface is said to be a surface of 1,000 – 2,000 square Angstroms, so putting a few amino acids in the surface can change things radically.   Not only that, but alanine scanning of the interfaces shows that only a small set of ‘hot spot’ amino acids contribute to the free energy of binding at the protein/protein interface.  (Hot spots are operationally defined as an amino acid, that when mutated to alanine leads to a greater than 10fold drop in the binding constant).  Let’s hear it for the blind watchmaker for figuring out a way to accelerate evolution by moderating protein protein interactions directly.

It is interesting  that the vast majority of microexons contain multiples of 3 nucleotides (this prevents them from producing a frameshift in the mRNA in which they are found).  This implies that natural selection is at work on them.

Most microExons show high inclusion rates at late stages of neuronal differentiation in genes associated with axon formation and synapse function.  One example — a neural specific microExon in Protrudin increases its interaction with Vesicle Associated Membrane protein VAMP) to promote neurite outgrowth.

A protein called SRRM4 controls the inclusion of most neuronal microexons known so far.  Of all known tissue types the human retina has the largest program of tissue enriched microExons .  Some of these microexons are found only in photoreceptor cells. Ectopic expression of SRRM4 is enough to drive the inclusion of most retinal microExons in nonphotorector cells.

For lots of current references on microExons, particularly those in the retina, please see Proc. Natl. Acad. Sci. vol. 119 e2117090119 ’22

I haven’t been posting for a while because of a computer disaster.  All of the notes I’ve taken on the literature and elsewhere were on an old iMac running HyperCard (which just crashed). As my son was told at USC, there are two types of disc drives.  Those that have crashed, and those that haven’t crashed (yet).  I’ve got another one, but I’m busy programming to transfer the data and metadata to Mathematica.  There is plenty to post about, which should be forthcoming.