Living things, from bacteria to humans, depend on a workforce ofproteins to carry out essential tasks within their cells. Proteinsare chains of amino acids that are strung together according toinstructions encoded within that most important of molecules -DNA.
The string of "letters" that make up DNA correspond to chains ofamino acids, and they are read in threes, with every combinationrepresenting one of many amino acids. Until now, scientistsbelieved that this relationship is unambiguous - within any singlegenome, every three-letter combination maps to one and only oneamino acid. This strict one-to-one relationship is a tenet ofgenetics, but new research shows that it's not an absolute one.
A team of American scientists have found a surprising exceptionto this rule, within a sea microbe called Euplotes crassus. In itsgenome, one particular triplet of DNA letters can stand for one oftwo different amino acids - cysteine or selenocysteine - evenwithin the same gene. It all depends on context. This is the firsttime that such dual-coding has been spotted in the genes of anyliving thing.
Genetics 101
Before I go any further, it's probably a good idea to have aquick primer on the genetic code for non-scientists. Anyone withprior knowledge of genetics can just skip the next four paragraphs.DNA is a chain of four molecules called nucleotides - adenine,cytosine, guanine and thymine, represented by the letter A, C, Gand T. These sequences are transcribed into a similar moleculecalled messenger RNA (mRNA), which contains three of the samenucleotides, but replaces thymine with uracil (U). It's theinformation coded by mRNA that is finally translated intoproteins.
Proteins are built from 20 different amino acids, chainedtogether in various combinations. In mRNA, every three letterscorresponds to a specific amino acid. These three-lettercombinations are called "codons", the genetic equivalent of words.For example, the codon CCC (three cytosines in a row) correspondsto the amino acid proline, while AAA (three alanines) correspondsto lysine. And some codons act as full-stops, indicating that theamino acid chain has come to an end.
This genetic code is almost universal. The same codons almostalways match up to the same amino acids in tiny bacteria, talltrees and thoughtful humans. There are a few deviations from theuniversal template, but even then, the differences are relativelyminor. Think about computer keyboards - almost all have the sameconfiguration of keys for various letters and symbols, but somewill have the @ key in a different place.
The genetic code is redundant, so that several codons representthe same single amino acid, but there are no ambiguities. There areno examples of a single codon within any genome that representsmore than one amino acid. That is, until now.
The Euplotes crassus Code
Anton Turanov, Alexey Lubanov and Vladimir Gladyshev from theUniversity of Nebraska have discovered that in Euplotes crassus,the UGA codon can mean either cysteine or selenocysteine, dependingon its location in the gene.
In the universal code, UGA is a stop signal but many species useit to signify selenocysteine, an amino acid that isn't representedin the universal code. This alternative translation of UGA intoselenocysteine hinges on a structure called a SECIS element. TheSECIS is part of the mRNA molecule itself but sits outside theregion that actually codes for amino acids. It's like a geneticShift key - its presence changes the meaning of UGA codons that sitbefore it.
What makes E.crassus unique is the fact that its UGA codons canmean either selenocysteine or cysteine - a choice between two aminoacids rather than one amino acid and a stop signal.
Turanov and Lubanov analysed the microbe's tRNAs -molecules withone end that recognises a specific codon and another that sticks toits corresponding amino acid. These are the decoders that translatestrings of codons into strings of amino acids. It turned out thatE.crassus has different tRNAs that recognise UGA - one of thesematches the codon with cysteine and another matches it withselenocysteine.
Turanov and Lubanov also purified a protein from E.crassuscalled Tr1. Its RNA has a SECIS element and five UGA codons, andthe duo found that the first four of these are translated intocysteines and the fifth into selenocysteine. Location isall-important when it comes to working out which interpretationcomes out top. When Turanov and Lubanov added lots of UGA codons atsites throughout the TR1 gene, they found the vast majority weretranslated into cysteines. Only those inserted at the end of thegene, within its final 20 codons and near the SECIS element, wereinterpreted as selenocysteines.
So the SECIS element, in its Shift-key role, affects the fate ofnearby UGAs. To confirm that, Turanov and Lubanov replaced theentire SECIS element in the TR1 gene with an equivalent elementfrom a different gene and a different species. They found that thisnew SECIS element had a wider zone of influence; when it wasintroduced, UGA codons that sat outside the final 20 weretranslated into selenocysteines instead of cysteines.
So in E.crassus, the UGA codon is not tied to a single fate - ithas a choice. It can be interpreted in two different ways,depending on its location and that of the SECIS element thatinfluences it. One codon, two amino acids - it's a unique set-upand further proof that the genetic code, universal though it almostis, is open to expansion and evolutionary change.
Reference: A. A. Turanov, A. V. Lobanov, D. E. Fomenko, H. G.Morrison, M. L. Sogin, L. A. Klobutcher, D. L. Hatfield, V. N.Gladyshev (2009). Genetic Code Supports Targeted Insertion of TwoAmino Acids by One Codon Science, 323 (5911), 259-261 DOI:10.1126/science.1164748
