Sixteen years after the discovery of the 21st amino acid encoded by DNA, scientists have found another of these basic protein building-blocks encoded in the genes of methane-manufacturing bacteria found in the stomach of cows. The discovery suggests that the genetic code may be more flexible than researchers previously believed.
In the early 1960s, scientists cracked the genetic code when they learned that the four DNA bases--A, T, G, and C-- were assembled into 64 unique three-letter words, or codons. Researchers originally thought that the codons might represent all the known amino acids, which ribosomes inside cells string together into proteins. But as it turns out, cells have codon codes for only 20 amino acids and for simple commands like "stop"--which tells the ribosomes to stop building a protein chain. Other rare amino acids found in proteins are made by tinkering with members of the original 20 after they have been daisy-chained onto a protein. These oddball amino acids aren't encoded in DNA.
The 22nd amino acid, pyrrolysine, is different. A modified form of lysine--one of the 20 common amino acids--pyrrolysine has its own codon, for which it has appropriated one of DNA's three stop codons. Like other encoded amino acids, it uses a specialized transfer RNA molecule to carry it to the ribosome. Joe Krzycki and colleagues at Ohio State University in Columbus report the discovery of the new amino acid, its codon, and the specialized tRNA in the 24 May issue of Science.
How did "stop" come to mean "add pyrrolysine"? Geneticist John Atkins of the University of Utah in Salt Lake City suggests it may be partly because the ribosomal machinery takes extra time to process a stop codon. The protein assembly system can add 60 amino acids to a protein chain in the time it takes to obey one "stop" command, he says. Normally, encountering a pyrrolysine/stop codon would shut down the mechanism. But the added time gives the tRNA attached to pyrrolysine a chance to nip in and plug itself into the stop codon, an action that adds pyrrolysine to the end of the chain and restarts the chain-building process. The take-home message, Atkins says, "is that there's a diversity and richness in the decoding process," and more flexibility than the original DNA decoders expected in the machinery of protein construction.