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?

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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]