The death of the synonymous codon – II

Actin and myosin are the two main muscle proteins which let us move about.  However all cells contain actin whether they move or not. Actin comes in 6 closely related forms (isoforms), the products of 6 different genes. 4 actins are found only in muscle cells (smooth, striated, cardiac).   The other two actins (the beta and gamma isoforms of actin) are found in nearly every cell, motile or not. In man beta and gamma actin  are the product of different genes on different chromosomes.  Despite that,  the amino acid sequence of the two is 98% identical. Yet there is usually a lot more beta actin in a given cell than gamma actin.  What gives?

If you’ve been following the series, read on, otherwise the background you need can be found in the 3 posts of “Molecular biology survival guide for chemists” particularly the third and  recent post “The death of the synonymous codon”.   Actin contains 375 amino acids, beta and gamma differing only at 4 of them, all near the amino terminus of the protein. Even the differences aren’t chemically that great –the second amino acid from the amino terminal end of beta actin is aspartic acid, while in gamma actin it’s glutamic acid.  Big deal.  The other 3 amino acid differences are equally trivial (to the chemist at least).  Recall that proteins are synthesized in the ribosome starting with the amino terminal amino acid, adding the next successively.  So as a protein is being made, the amino terminal amino acid remains the same, while the carboxy terminal amino acid changes every time a new one is added.

The beta and gamma actin genes contain different synonymous codons for all but 4 of the amino terminal amino acids (which actually vary between beta and gamm actin).  It appears that the choice of codons for gamma actin results in slower synthesis of the protein by the ribosome.  Perhaps there is less tRNA or tRNA synthetase around for the codons used by the gamma actin gene.  The papers this is taken from don’t say [ Science vol. 329 pp. 1473 – 1474, 1534 – 1537 ’10 ].  The slower synthesis of gamma actin results in exposure of a lysine at codon #18, which is then modified (ubiquitinated) leading to it’s destruction.

The authors prove this by switching the ‘synonymous’ codons of gamma actin for those of beta actin, and vice versa.  What do you think happens?

After the switch, cells contain more gamma actin than beta actin.  So synonymous codons are far from synonymous.  This also shows the exquisite forms of biochemical control (and subtlety) found in the cell.

More importantly, this is  the exactly  where reductionism into chemical terms fails in explaining cellular events.  The philosophic implications (and I think they are huge) of this will be the subject of the next post.

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