Accordions and Molecular Evolution

[ Cell vol. 150 pp. 671 – 672, 831 – 841 ’12 ] Describes a remarkable mechanism of molecular evolution under selection pressure.  No one has picked it up till now because it removes traces of itself.  Essentially the genome expands and contracts like an accordion.  But first a joke.

By and large classical musicians loathe the accordion.  So naturally at a chamber music get together for amateurs we were surprised when, at the opening meeting, the organizer told us that one of the piano coaches (Cary Lewis) actually loved the accordion and taught people how to play it.  He would go to the roughest neighborhoods to bring accordion knowledge to the masses.  One dark night, he parked his car leaving a spare accordion in it while he went inside to give a lesson.  When he came out he found the windshield smashed and inside — 3 more accordions.

The system described in Cell involves a poxvirus (vaccinia –used to vaccinate against smallpox, another poxvirus).  Cells have all sorts of viral defenses, on of which is called PKR (the actual mechanism is irrelevant).  Vaccinia has a protein called K3L which rather ineffectively negates the PKR effect (the mechanism is irrelevant).

The virus responds to this selection pressure by producing additional copies of the K3L gene, which means that the virus makes more of it when infecting a cell, increasing resistance.  If selection is relaxed (which happens in a permissive host), the K3L gene copy number drops — it takes a lot of metabolic energy to make more DNA.

If selection continues, eventually a rare mutation occurs in one of the gene copies of K3L, making it more effective in combating PKR.  When this happens the copy number of the K3L gene drops leaving the more effective variant as the only gene.

Essentially the K3L gene is expanding and contracting like an accordion in response to selection pressure.  The expansion allows far more rapid evolution of an effective response to PKR than would happen with a single copy.

The interesting point, is that once contraction occurs, there is no trace of the accordion mechanism left in the genome, just a more effective protein.  The same process has been shown to generate antibiotic resistance, and to explain the evolution of enzymes (in bacteria) that degrade man-made pollutants.

Whether accordions occur in our genome isn’t known.  Even if it doesn’t normally, it likely does occur in cancer cells. Similarly, whether accordions explain the emergence of genes with new functions from old ones isn’t known, but people are sure to be working to find out.

Just another reason to keep reading the literature.  There is always something new and unexpected.  Shakespeare knew this years ago.

There are more things in heaven and earth, Horatio,
Than are dreamt of in your philosophy.
– Hamlet (1.5.166-7), Hamlet to Horatio

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