'Fishy' clue helps establish how prote...( New Haven Conn. Three billion years...)

New Haven, Conn. Three billion years ago, a "new" amino acid was added to the alphabet of 20 that commonly make up proteins in organisms today. Now researchers at Yale and the University of Tokyo have demonstrated how this rare amino acid and, by example, other amino acids made its way into the menu for protein synthesis. The study appeared in the December 31 advance online publication of the journal Nature.

The rare amino acid the Yale researchers studied, pyrrolysine (Pyl), gave the researchers a molecular handle by being an extreme example of an amino acid that evolved to serve a highly specific need.

The amino acid alphabet shapes the language of proteins. When the genetic code was deciphered four decades ago, scientists believed that there were no more than 20 amino acid "letters" that universally meshed with the nucleic acid part of the protein code. But, like many alphabets, the language of proteins has letters with modifications like accent marks that modify their use.

When cells make proteins, a tightly coordinated pair of molecules a tRNA and a tRNA synthetase ensure that the correct amino acid is added in a growing protein chain. These molecules are highly specific for the amino acid they "manage" and are coded directly in the genome. All of the 20 common amino acids are incorporated into proteins in this way. However, only two uncommon amino acids, including Pyl, have been discovered that follow this pattern.

In most cases, an uncommon amino acid in proteins like letters with accent marks results from modification of one of the standard 20 amino acids after it has become part of the protein. Many human proteins are modified in this way, and deficiencies in these modifications are linked to myriad human diseases including cancer, neurodegeneration, and metabolic disorders.

"Pyl turns out to be special because it represents an uncommon amino acid that is incorporated during normal protei
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