So much for 1 codon = 1 amino acid

[Paul C. Anagnostopoulos]

The January 9 issue of Science includes an article titled "Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon." The authors describe the ciliated protozoa E. crassus, in which the amino acid cysteine is encoded in mRNA by the three codons UGA, UGU, and UGC. However, UGA also codes for selenocysteine, the "21st amino acid."

UGA codes for cysteine unless a SECIS element appears in the mRNA, in which case it codes for selenocysteine. The location of the SECIS element varies with the type of organism, sometimes appearing immediately following the UGA codon, sometimes at the 3' end of the mRNA, sometimes at the 5' end. When it is present, UGA codes for selenocysteine rather than cysteine.

But now the cool part. In certain E. crassus mRNAs, such as that for the eTR1 gene, UGA appears multiple times and codes for selenocysteine in one or two cases, but cysteine in all other cases. The SECIS element only causes selenocysteine translation when UGA codons appear in certain positions of the mRNA.

The same codon codes for two different amino acids in the same gene. Nature finds a way to extend the genetic coding system. So much for another bit of biological dogma.

~~ Paul

[sol invictus]

I thought things like that were well known. For example, some viruses use the same bit of D/RNA to code for up to three different proteins, by offsetting the start of the sequence by 0, 1 or 2 nucleotides.

[Dymanic]

Nature finds a way to extend the genetic coding system.That sort of thing never SECIS to amaze me.

[paiute]

The Prophet Lehninger wrote that at his right hand he saw three nucleotides and on the left hand he saw a single amino acid burning bright. Your post is heresy. Report to the city gates for your stoning.

[Ixion]

I thought things like that were well known. For example, some viruses use the same bit of D/RNA to code for up to three different proteins, by offsetting the start of the sequence by 0, 1 or 2 nucleotides.

This is not the same as what Paul is speaking of in the OP. What you are referring to is called frame-shifting, and it is a common method of regulation in viruses, but also in higher organisms.

In the OP, the amino acid cysteine is usually coded by the RNA UGA (which is supposed to be specific for the amino acid). However, the authors of the paper discovered that certain cis-acting elements (meaning codes within the mRNA of the organism E. crassus in this example) result in the insertion of a selenocysteine at particular UGA codons, instead of the typical cysteine. This is an important find because, although it had been speculated that cis-acting elements could influence translational differences in organisms, it had never been empirically observed. :)

[Paul C. Anagnostopoulos]

What was known previously was that the stop codon sometimes codes for an amino acid. Also that UGA codes for cysteine in some genes and selenocysteine in others. The new marvel is that UGA can code for both amino acids in the same gene.

It's chemistry: Whatever works, works.

~~ Paul

[sol invictus]

This is not the same as what Paul is speaking of in the OP.

I see - thanks for the clear explanation.

[Ixion]

I see - thanks for the clear explanation.

You are welcome (I really do hope that I made it clear...if not, please let me know and I will try again). :D

[joobz]

This isn't that shocking.

The Tirrell group from Caltech has been exploiting bacteria to produce synthetic polypeptides composed of "non-canonical" amino acids. They'll starve bacteria of a natual amino acid and substitute the culture with a synthetic analog (e..g,replace methioine with an azide containing peptide).

It only makes sense that if we can do this artificially in the lab, then the mechanism could also happen in nature.


ETA: This was one of the cool ones, where they made a flourinated analog of GFP. The native protein lost much of it's flourescence, but they then "evolved" mutants which allowed them to restore flourescence in the flourinated form.

http://www.pnas.org/content/104/35/13887.full?ck=nck

[mijopaalmc]

Here's the abstract:
Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon
Anton A. Turanov,1* Alexey V. Lobanov,1* Dmitri E. Fomenko,1 Hilary G. Morrison,2 Mitchell L. Sogin,2 Lawrence A. Klobutcher,3 Dolph L. Hatfield,4 Vadim N. Gladyshev1{dagger}

Strict one-to-one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3' untranslated region structure and location of the dual-function codon within the messenger RNA (mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location-dependent dual function of UGA when expressed in mammalian cells. Thus, the genetic code supports the use of one codon to code for multiple amino acids.

1 Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.
2 Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA 02543, USA.
3 Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT 06032, USA.
4 Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

This just doesn't seem that novel though. For instance, the Wikipedia article on selenocysteine (http://en.wikipedia.org/wiki/Selenocysteine) has references on selenocysteine insertion from the 1970's and 1980's.

[Ixion]

In the earlier cases, maybe they just didn't look hard enough to realize that the SECIS could encode for either cysteine or selenocysteine? The differences are slight within the actual biochemistry of the amino acid, so it could be that the differences were not easily resolved with the technologies of the 1980s, or that it simply was overlooked without realizing it. I am not overly surprised by the find, but it is an interesting challenge to biological dogma that was not empirically addressed until now.

As an interesting side note, the scientist that "discovered" the stop codon, Harris Bernstein, is a professor in my department at the University of Arizona. I think he is mostly retired now, but it would be interesting to see what his take on this find would be.

[Paul C. Anagnostopoulos]

This just doesn't seem that novel though. For instance, the Wikipedia article on selenocysteine has references on selenocysteine insertion from the 1970's and 1980's.
The new thing here is that UGA codes for both cysteine and selenocysteine in the same gene. It's not super-surprising, but it is cool.

~~ Paul