Tuesday, April 5, 2011

Mike Gene takes the Challenge

Over at Design Matrix, Mike Gene has responded to John's challenge that the start codon is an inefficient design (I was hoping Mike would, since he has more knowledge of biology in his little finger than I do in my very overweight body):

"Y’see the start codon has an important job not shared by any other codon – it sets the reading frame. If you want a translation system that does not encode an amino acid for its start codon, you’ll need a completely different mechanism to set the reading frame. Has anyone ever proposed such a mechanism? And if so, is there any evidence that such a system would do a better job at setting the proper reading frame? Until those questions can be answered, no problem has been demonstrated with using the start codon to code for an amino acid.

But what about your claim that “methionine often interferes with the correct folding of the protein?” Really? How often is often?

The second process that removes the methionine from many proteins is known as methionine excision and depends on the protein methionine aminopeptidase. You say that it seems needlessly inefficient, but again, think design tradeoffs and remember that efficiency is not the sole criterion of good design.

So at this point I would direct your attention to something called the N-end rule. Here is a review paper written by the scientist who uncovered this rule.


It basically states the N-terminal amino acid plays a key role in determining the half-life of a protein. If you look at table 1, you’ll see that a protein whose first amino acid is methionine has a half-life of 30 hours. If it was tyrosine, it would be 10 minutes. And if you check out figure 1, you’ll see that methionine is considered a stabilizing residue (one of the three universal stabilizing residues). So the start codon represents a default state for giving a protein a long lifespan. By cutting away the methionine, the cell can in effect set the lifespan of the newly made protein that is shorter. Looks pretty elegant to me.

But there is more meaty stuff to get out of the N end rule."

Let's hope he writes about the more meaty stuff.

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