A discovery by UNL researchers expands understanding of the genetic code, and may help revise a tenet of this universal language of life.

In cells, the genetic code essentially provides instructions for creating proteins, the basic structural molecules of life. The code includes a series of unique three-letter “code words,” called codons. These genetic passwords dictate insertion of amino acids, the building blocks of proteins. While codons may change to code for different amino acids in different organisms, a long-held precept of the genetic code is that one codon provides the password only for one amino acid in an organism.

Not always, UNL scientists discovered.

RESEARCH TEAM – Members of the UNL research team that made the genetic code discovery include, from left, Alexey Lobanov, senior research associate who handled the computing analysis; Anton Turanov, former graduate student who did much of the experimental work; and Vadim Gladyshev, professor of biochemistry. Photo by Joel Brehm/Office of Research.

“We showed that one codon may code for two amino acids, even within the same gene. That’s really unexpected,” said Vadim Gladyshev, the biochemistry professor whose team made the discovery.

Other members of the team from UNL include Anton Turanov, a graduate student at the time of the research; Alexey Lobanov, senior research associate; and Dmitri Fomenko, assistant professor of biochemistry.

The team and other collaborators reported the findings in the Jan. 10 issue of the international journal Science.

Their discovery of the multi-tasking codon, called UGA, in the microscopic marine protozoan, Euplotes crassus, raises the question of whether codons in other organisms can do the same thing. They’re now investigating UGA’s function in mammals.

“If the two-amino acid function of a codon evolved in one organism, it might exist in other organisms, too. It raises lots of questions and possibilities,” Gladyshev said. “Nobody even considered that a particular codon could specify multiple amino acids. Our work suggests it’s possible so it needs to be checked out in other organisms, including humans.”

Gladyshev’s team studies selenoproteins and selenium to understand their role in human health. In humans, the UGA codon is a password for selenocysteine, the amino acid that helps create selenoproteins. It’s been known that the protozoan Euplotes uses UGA to code for cysteine.

“We were just curious” whether this micorogranism produced selenocysteine and, if so, what codon was used for this amino acid, he said.

To find out, the team had to sequence the protozoan’s entire genome, which required samples of the organism as well as extensive computer analysis and lab work. Lawrence Klobutcher, a professor at the University of Connecticut Health Center, provided the protozoan material and expertise in this organism. Lobanov, a bioinformatics expert, handled the computing while Turanov, an expert in experimental procedures, did the lab work. They discovered that in this protozoan, UGA can code for either cysteine or selenocysteine, even within the same gene. Which amino acid gets inserted depends on the location of UGA within the gene and proximity of an RNA element that signals UGA to insert selenocysteine.

Previously, scientists thought that if the RNA element was present, UGA would insert selenocysteine. “Now we found that not every position in the gene supports selenocysteine,” Gladyshev said, which could have implications for the role of selenium in mammals.

“It’s well known that a specific codon does different things in different organisms. The novelty of our work is that we found this codon can do multiple things in a single organism,” he added.

Other collaborators on the Science paper were Klobutcher, Dolph Hatfield of the National Cancer Institute at the National Institutes of Health, and Hilary Morrison and Mitchell Sogin, both of the Marine Biological Laboratory, Woods Hole, Mass. Grants from the NIH fund Gladyshev’s research.