The First Genetic Word

Prof. Edward Trifonov is a detective -- but you won't find him at the scene of any crime. Trifonov, a member of the Weizmann Institute's Structural Biology Department, is a molecular geneticist and in his latest "case" he appears to have discovered the very first genetic sequence -- the first "word" in the genetic code of all living matter.

 

"We are all full of sequences," says Trifonov. "Life itself began as sequences. The original idea was that if some features of those ancient sequences remain in our genes today, perhaps we could track them down."

 

To reconstruct this molecular evolution, Trifonov turned not to the laboratory but to advanced mathematical and statistical analysis. He and a German colleague, Dr. Thomas Bettecken, first studied the nucleotide triplets that make up the genetic code in DNA and RNA. Could they find out which were the most ancient of the nucleotide triplets in our past? They soon realized that the occurrence of triplets led by the letter G (each nucleotide is signified by a letter) was frequent both in older patterns and in the patterns of modern genes. "You'd expect that in natural sequences a quarter of the cases would begin with G, while actually a third of all triplets start with G. This was a very strong lead to their original state," Trifonov explains.

 

Continuing to analyze the data, the team came to the conclusion that the triplet GCT is the most common and also the most expandable triplet. Therefore, it is the most likely candidate to be the earliest. "We realized that as soon as you give the triplet a chance to copy itself, it not only makes copies but makes them longer. GCT races to expand itself," Trifonov explains.

 

The researchers understood right away, however, that you could not produce a protein with just one repeating triplet. "That would be too monotonous: It wouldn't lead to life." But what if the triplet started to mutate? "Altogether, this would lead to ten triplets," says Trifonov. "And then we made a bold speculation that these ten triplets were the first coding triplets ever formed."

 

Trifonov and Bettecken then followed their next lead, this time aiming to unearth the list of the most ancient primordial amino acids, the building blocks of life. The team's first list of candidates had to meet the criterion of being amino acids that have a simple chemical structure. Then, recruiting one more criterion, Trifonov and Bettecken were able to reconstruct a list of the seven presumably earliest amino acids. All of them turned out to be encoded by the triplets derived from the starting GCT. In addition, the amino acid that corresponds to this generic triplet was also on the list.

 

The next step involved applying several more amino acid criteria. In this step, Trifonov estimated the chronological order in which the amino acids had appeared on life's stage, by averaging the orders suggested by the criteria.

 

Trifonov studied electrical engineering at Moscow Physical Technical Institute. In 1976, Trifonov and his family emigrated to Israel after only one year as refuseniks, this despite the fact that he had worked at the Moscow Atomic Energy Institute (albeit in a nonsecret biological division). "The Israeli Security Service thought at first that I was a spy," Trifonov recalls with a smile. And, although somewhat shy about the coverage his research has garnered, this Sherlock Holmes has finally caught his elusive evolutionary "culprit."