New word in life's lexicon

JOHN WHITFIELD

There's a new word to life's vocabulary. DNA letters can be rearranged to spell out a 22nd amino acid, researchers have discovered.

DNA: the letters of life have more permutations than we thought. © Getty Images

The scientists who cracked life's genetic code in the 1950s said that it writes a mere 20 'words' - the amino acids from which the myriad proteins in all life are built. But in 1986 another amino acid was discovered in bacteria.

"We thought the 21st was an aberration, but here we see another one," says biochemist Michael Chan of Ohio State University, Columbus. "Perhaps 23 and 24 are just around the corner."

Amino acids 21 and 22 do not have genetic code of their own. They are put into proteins by a change in the meaning of a DNA sequence that normally halts protein manufacture.

Chan and his colleagues found the new amino acid, called pyrrolysine, in a microbe called Methanosarcina. The bug lives in cattle guts where it breaks down organic molecules for energy, making methane as a by-product. Pyrrolysine is in one of the organism's methane-producing proteins^1,2.

The Ohio team also found a gene for a pyrrolysine-containing protein in a bacterium, but the amino acid is probably not widespread, says geneticist John Atkins of the University of Utah, Salt Lake City. By contrast, the 21st amino acid, selenocysteine, pops up in many organisms from bacteria to mammals.

The discovery highlights the flexibility of cell machinery, says Atkins. "There's a greater richness in reading the genetic code than many people had appreciated," he says.

Chain of events

Proteins are chains of amino acids. The sequence of DNA letters in genes determines the order of amino acids.

Each three-letter DNA sequence spells one amino acid. There are four different DNA letters, or bases, giving 64 possible three-base combinations, so some amino acids have more than one triplet spelling.

It takes several steps to turn the information in the genome into protein. First, a gene is copied into a molecule called messenger RNA that moves from the cell's chromosome to its protein factory.

Then other molecules called transfer RNAs, which carry the amino acids, attach to the messenger RNA. There are transfer RNAs for every three-letter code word, except those that stop protein synthesis. As they line up on the messenger RNA, the amino-acid chain forms, before detaching to become a fully fledged protein.

Methanosarcina has tinkered with this machinery extensively to allow it to use pyrrolysine. The bug has to make the molecule, probably by modifying one of the 20 core amino acids, and also to create a special transfer RNA to bear it. And at some point during evolution the meaning of a DNA code word has changed from 'stop' to 'pyrrolysine'.

How this switch might have come about isn't known. One clue, says Atkins, is that the cellular machinery takes 2 seconds to read the 'stop' code but just 30 milliseconds to process those representing ordinary amino acids. This delay might give a modified transfer RNA the chance to nip in and take the place of the molecule that usually terminates the protein chain.

1. Srinivasan, G. James, C. M. & Krzycki, J. A. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science, 296, 1459 - 1462, (2002).
2. Hao, B. et al. A new UAG-encoded residue in the structure of a methanogen methyltransferase. Science, 296, 1462 - 1466, (2002).

© Nature News Service / Macmillan Magazines Ltd 2002