Study offers insight into the origin of the genetic code

Aug 26, 2013
Study offers insight into the origin of the genetic code, team reports
Graduate student Derek Caetano-Anollés, crop sciences and Institute for Genomic Biology professor Gustavo Caetano-Anollés and senior bioinformatician Minglei Wang report that the emergence of the genetic code corresponds to the advent of protein flexibility. Credit: L. Brian Stauffer

An analysis of enzymes that load amino acids onto transfer RNAs—an operation at the heart of protein translation—offers new insights into the evolutionary origins of the modern genetic code, researchers report. Their findings appear in the journal PLOS ONE.

The researchers focused on aminoacyl tRNA synthetases, enzymes that "read" the genetic information embedded in transfer RNA molecules and attach the appropriate amino acids to those tRNAs. Once a tRNA is charged with its amino acid, it carries it to the , a cellular "workbench" on which proteins are assembled, one amino acid at a time.

Synthetases charge the amino acids with high-energy that speed the later formation of new peptide (protein) bonds. Synthetases also have powerful editing capabilities; if the wrong amino acid is added to a tRNA, the enzyme quickly dissolves the bond.

"Synthetases are key interpreters and arbitrators of how nucleic-acid information translates into amino-acid information," said Gustavo Caetano-Anollés, a University of Illinois professor of and of bioinformatics. Caetano-Anollés, who led the research, also is a professor in the U. of I. Institute for Genomic Biology. "Their editing capabilities are about 100-fold more rigorous than the proofreading and recognition that occurs in the ribosome. Consequently, synthetases are responsible for establishing the rules of the genetic code."

The researchers used an approach developed in the Caetano-Anollés lab to determine the relative ages of different protein regions, called domains. Protein domains are the gears, springs and motors that work together to keep the running.

Caetano-Anollés and his colleagues have spent years elucidating the evolution of protein and RNA domains, determining their relative ages by analyzing their utilization in organisms from every branch of the tree of life. The researchers make a simple assumption: Domains that appear in only a few organisms or groups of organisms are likely younger than domains that are more widely employed. The most universally utilized domains—those that appear in organisms from every branch of the tree of life—are likely the most ancient.

The researchers used their census of protein domains to establish the relative ages of the domains that make up the synthetases. They found that those domains that load amino acids onto the tRNAs (and edit them when mistakes are made) are more ancient than the domains that recognize the region on the tRNA, called an anticodon, that tells the synthetase which amino acid that tRNA should carry.

"Remarkably, we also found that the most ancient domains of the synthetases were structurally analogous to modern enzymes that are involved in non-ribosomal protein synthesis, and to other enzymes that are capable of making dipeptides," Caetano-Anollés said.

The researchers hypothesize that ancient protein synthesis involved enzymes that looked a lot like today's synthetases, perhaps working in conjunction with ancient tRNAs.

Researchers have known for decades that rudimentary protein synthesis can occur without the involvement of the ribosome, Caetano-Anollés said. But few if any have looked to the enzymes that catalyze these reactions for evidence of the of protein synthesis.

Alerted to the potential importance of dipeptide formation in early protein synthesis, the researchers next looked for patterns of frequently used dipeptides in the sequences of modern proteins. They focused only on proteins for which scientists have collected the most complete and accurate structural information.

"The analysis revealed an astonishing fact," Caetano-Anollés said. "The most ancient were enriched in dipeptides with encoded by the most ancient synthetases. And these ancient dipeptides were present in rigid regions of the proteins."

The domains that appeared after the emergence of the genetic code (which Caetano-Anollés ties to the emergence of the tRNA anticodon) "were enriched in dipeptides that were present in highly flexible regions," he said.

Thus, genetics is associated with protein flexibility, he said.

"Our study offers an explanation for why there is a ," Caetano-Anollés said. Genetics allowed proteins "to become flexible, thereby gaining a world of new molecular functions."

Explore further: Bitter food but good medicine from cucumber genetics

More information: The paper, "Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Impact of Protein Flexibility," is available online. www.plosone.org/article/info%3… journal.pone.0072225

Related Stories

Study of giant viruses shakes up tree of life

Sep 13, 2012

A new study of giant viruses supports the idea that viruses are ancient living organisms and not inanimate molecular remnants run amok, as some scientists have argued. The study reshapes the universal family ...

Untangling life's origins

Mar 11, 2013

Researchers in the Evolutionary Bioinformatics Laboratory at the University of Illinois in collaboration with German scientists have been using bioinformatics techniques to probe the world of proteins for answers to questions ...

Study reveals key step in protein synthesis

Jun 27, 2013

Scientists at the University of California, Santa Cruz, have trapped the ribosome, a protein-building molecular machine essential to all life, in a key transitional state that has long eluded researchers. Now, for the first ...

Biologists uncover a novel cellular proofreading mechanism

Nov 11, 2011

(PhysOrg.com) -- To make proteins, cells assemble long chains of amino acids, based on genetic instructions from DNA. That construction takes place in a tiny cellular structure called a ribosome, to which amino acids are ...

Copycat protein finds a perfect match

Nov 19, 2010

As proteins are synthesized during messenger RNA translation, fresh amino acids are delivered to the ribosome of the cell by nucleic acid molecules known as transfer RNAs (tRNAs). Each amino acid has a cognate ...

Recommended for you

Bitter food but good medicine from cucumber genetics

19 hours ago

High-tech genomics and traditional Chinese medicine come together as researchers identify the genes responsible for the intense bitter taste of wild cucumbers. Taming this bitterness made cucumber, pumpkin ...

New button mushroom varieties need better protection

Nov 27, 2014

A working group has recently been formed to work on a better protection of button mushroom varieties. It's activities are firstly directed to generate consensus among the spawn/breeding companies to consider ...

Cataloguing 10 million human gut microbial genes

Nov 25, 2014

Over the past several years, research on bacteria in the digestive tract (gut microbiome) has confirmed the major role they play in our health. An international consortium, in which INRA participates, has developed the most ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.