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Friday, January 09, 2009

A Shocking Discovery

Almost all proteins in Escherichia coli begin with the amino acid N-formylmethionine (f-met), a modified version of methionine.

N-formylmethionine is inserted at AUG codons at the beginning of the open reading frame in mRNA. The initiation mechanism requires a specific initiator tRNA called f-Met-tRNA (right).

Internal AUG codons are recognized by another tRNA and normal methionine is inserted at these positions. The observation that a single codon (AUG) can serve as the codeword for two different amino acids depending on their position was made over thirty-five years ago and it has been incorporated into the textbooks for decades.

You can imagine how surprised I was to read this in a press release written by Haley Stephenson of ScienceNOW Daily News. You can read it yourself on the Science website: Genetic Code Sees Double.
Call it the genetic version of a double-entendre. Scientific dogma dictates that various three-letter combinations of our genetic sequence each "mean" exactly one thing--each codes for a particular amino acid, the building block of proteins. But a protozoan named Euplotes crassus appears to be more versatile: One of its three-letter combinations has two meanings, coding for two different amino acids. Although the find may seem trivial, it poses a major challenge to more than 4 decades of scientific thinking.
The idea that a protozoan might use UGA to encode both cysteine and a modified form of serine called selenocysteine is quite interesting. It has long been known that UGA is a normal stop codon that is also used to encode selenocysteine. It has also been known for a long time that some organisms can use UGA to encode cysteine.

But the idea that scientific dogma has been overturned by the discovery of a single codon that can encode two different amino acids is just plain silly. It doesn't pose a "major challenge to more than 4 decades of scientific thinking" unless your scientific thinking is flawed to begin with.

This must be an example of hyperbole. Such a claim would never make it into a scientific publication, especially in a prestigious journal like Science. Or so I thought.

Here's the opening sentence in the paper by Turanov et al. (2009).
Although codons can be recoded to specify other amino acids or to have ambiguous meanings (1, 2), and stop codons can be suppressed to insert amino acids (3), insertion of different amino acids into separate positions within nascent polypeptides by the same codeword is believed to be inconsistent with ribosome-based protein synthesis.
It's enough to make me give up writing biochemistry textbooks. Apparently nobody reads them.

We seem to be producing a generation of scientists who don't know about the fundamentals of biochemistry and molecular biology that were elucidated in bacteria and bacteriophage in the mid-20th century. Doesn't anyone teach this stuff any more?

Turanov, A.A., Lobanov, A.V., Fomenko, D.E., Morrison, H.G., Sogin, M.L., Klobutcher, L.A., Hatfield, D.L., and Gladyshev. V.N. (2009) Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon. Science 323:259-261. [DOI: 10.1126/science.1164748]


  1. There is apparently a lot of lazy writing/editing out there. So many stories with the "man bites dogma" theme, when scientific inquiry is really the very opposite of received authority.

    Why no placards in the offices of editors, or whoever is in charge of editors, saying never to allow words or themes like "revolutionary" or "overturns accepted wisdom" in the stories that cross their desks? Even if something that *is* revolutionary comes to them, understatement serves far better than overstatement in any scientific publication worthy of the name.

  2. Maybe Larry, you should wonder WHY does it happen that people forget that a single codon can serve as the codeword for two different amino acids depending on their position. Probably since this fact was discovered 35 years ago, there has been a tendency to sweep it under the rug as exceptional or merely anecdotal, much like you're doing right now with this new case (with the added downplaying argument that "we knew this all along"). Given your attitude, expect people to forget all about this new irrelevant case, too. You're certainly working towards that.

    Entertain the possibility taht the explanation is not the decadence of new science, as you're so fond of thinking. Perhaps, the expalantion is that biochemists still are much more fond of a rules than of an exception, and tend to wave them away as unimportant or anecdotal... and continue to do so.

  3. More regarding the novelty.
    From the Scientist:
    "But the paper's findings might not be all that novel, cautioned Yale University microbiologist Dieter Söll. He noted that in some Candida species, the CUG codon is translated as both leucine and serine, even in the same gene, albeit by a single ambiguous tRNA rather than two separate tRNAs as Gladyshev's team found in E. crassus. "This already showed that you can have the same codon in one gene [encode] two amino acids," Söll told The Scientist. "Really, it simply shows that nature has more than one way of doing the same thing." "