Breaking the Genetic Law

By Natalie Angier

Ever since the genetic code was cracked in the 1960s, biologists have believed the language of DNA to be rather like the Latin of the medieval church: universal, fundamental and indispensable. It seemed that all creatures, from men to mice to humble E. coli bacteria, shared the same basic instructions for making proteins, the building blocks of life; variations among organisms were thought to involve only the number and type of proteins that are strung together. Now researchers in the U.S., Europe and Japan have found species + that defy certain words in the genetic scripture: in the familiar Paramecium, a single-celled protozoan, and in a bacterium called Mycoplasma capricolum, the DNA patterns responsible for protein construction exhibit a surprising difference. Not only does the discovery undermine the "universality" of the genetic code, but it may cause scientists to rethink certain theories about evolution.

The double-helix DNA molecule, which is encased in the center of every living cell, is shaped like a spiral staircase. Each step in the staircase is composed of a compatible pair of four different nucleotides, rep- resented by the letters A, T, G and C. Grouped into sets of three steps, the nucleotides are called codons, which dictate, or code for, the 20 amino acids, the subunits of protein. A few codons, or code words, serve as punctuation marks, telling the cellular machinery to start or stop adding amino acids to the growing protein chain.

It was while studying the membrane of Paramecium that Biologist John Preer Jr. and his colleagues at Indiana University in Bloomington stumbled onto the aberrant code. In the midst of the long sequences of Paramecium codons, they kept finding words that in most creatures read "stop." Yet in Paramecium, the word added another amino acid. Says Preer: "We thought it must be an error in our technique." However, news soon filtered over from the Centre de Genetique Moleculaire laboratory near Paris that scientists there were encountering the same anomaly. As the two groups report in a recent issue of the British journal Na- ture, additional experiments showed that whenever the Paramecium's cellular machinery read either of two "periods" (TAG and TAA) in the standard code, it linked the amino acid glutamine onto the protein chain rather than stopping production; it obeyed only the third word for stop, TGA. At Nagoya University in Japan, scientists have found that Mycoplasma also ignores a stop triplet. But in this case it is TGA that is translated into an amino acid, tryptophan, while the other two codons are read as stop. "Within a certain sphere," says Biologist Syozo Osawa, "it seems that change is possible."

The latest revelations challenge certain assumptions of the so-called code- frozen accident theory postulated by Francis Crick, who with James Watson discovered the structure of DNA. Crick proposed that the genetic code was essentially an accident of nature, which, once fixed a few billion years ago, would never change. Explains Preer: "It's hard to imagine how one code could evolve into another without jeopardizing the protein in the cell." Whatever the mechanism, the changes must have occurred very early on; some biologists suggest that the alterations may have been a ploy by one-celled creatures to resist viruses, which destroy cells by invading them and taking over their cellular machinery.

For now, scientists are baffled and excited by the eccentric codes. They suspect that as they look ever deeper into the structure of DNA, they will find more examples of variation. "There are millions of organisms on the planet," says Osawa, "and only a handful have been examined genetically."

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With reporting by David Bjerklie/New York