Introns Facilitate Metazoan Complexity

Hopefully, you too can appreciate the brilliance and beauty of alternative splicing: 

Instead of three different, but similar, genes each with its own regulatory sequence and set of transcription factors, we more efficiently package it all into one gene/one promoter that is capable of making three different proteins.

So how would this process facilitate the evolution of metazoan life? Consider the picture below:

Source: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=dbio&part=A809

What this is telling you is that different cell types can express different versions of the same gene. And this is precisely the strategy that is used by the various cell types of your body (See my blog, “Why are there no prokaryotic mice?). Let me give you a classic example below the fold.

All of your cells possess the proteins actin and myosin.  Actin is a core cytoskeletal protein and myosin is the motor protein that travels along it.  In your muscles, many other proteins have organized and bundled the actin/myosin into thick protein capables that run the length of the muscle.  When stimulated, the cables shorten, resulting in the contraction of muscle.

One protein that works in conjunction with actin and myosin is a protein known as tropomyosin.  It binds to the actin and prevents myosin from binding when not needed.

Now closely survey the figure below as to see what happens with this tropmyosin gene in the different cells of your body:

Full size here

In this figure, the tropomyosin gene has 11 exons, but nowhere are they all used at the same time.  On the contrary, skeletal muscle, like you biceps muscle, does not use exon 2.  Smooth muscle, the muscle that lines your stomach and intestines, uses exon 2, but not exon 3 or 10.  Non-muscle tissue, like fibroblasts, liver, and brain, don’t use either exon 2 or 3 (those two must be muscle-specific).  But even among these, they differ: fibroblasts don’t use exon 10, liver does not use exon 7, and brain does not use exon 11.

Alternative splicing allows the body to fine-tune a single gene and its gene product to meet the unique needs of each cell in different types of tissue.  In other words, because of this process, you body can take any gene/protein and synthesis a brain-version, a stomach-version, a muscle-version, etc.  The proteins are all likely to have the same core function (note that all tropomyosin contain exons 1-4-5-6-8-9), but the activity, location, and specificity of each can be fine-tuned to fit the functional context of the different cell types.

It should now becoming 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 contraint of the same genome.

But would y’know it?  It get’s even better.

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3 responses to “Introns Facilitate Metazoan Complexity

  1. This is all very amazing. But now I’m beginning to wonder how the spliceosome “knows” which exons to use, and which ones to splice out.

  2. Pingback: Different Tunes in Different Tissues «

  3. Pingback: Set the Stage «

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