Could Life Use a Longer Genetic Code? Maybe, but It’s Unlikely

As diverse as life on Earth is, it can be anything from a jaguar hunting down a deer in the Amazon to a primitive cell in a hot springs in Canada. There are 64 three-letter words called codons, each of which stands for one of 20 amino acids. The proteins characteristic of each species is formed when the strands of the amino acids are strung together. All genomes have the same information.

A group of researchers at the Massachusetts Institute of Technology and Yale University showed in a new study that it is possible to modify one of these time-honored rules and create a more expansive, entirely new genetic code. Their discovery points to one of several ways of expanding the genetic code into a more versatile system that synthetic biologists could use to create cells with novel biochemistries. The work shows that an extended genetic code is hampered by its own complexity, becoming less efficient and even less capable in some ways, which may explain why life may not have favored longer codons in the first place.

It's not clear what these findings mean for life in other universes, but it's certain that our own genetic code evolved to be just right, and then ruled life for billions of years thereafter.

For example, with four-letter codons, there are more than 20 different possibilities, which might seem beneficial for life, because it would allow for the creation of more than 20 different types of proteins. It is possible to add a few quadruplet codons to the genetic code, but until now, no one has ever tried to create an entirely quadruplet genetic system.

The lead author of the new paper, who was a PhD student at MIT during the project, said that the study asked a genuine question.

Expanding on nature.

To test a quadruplet-codon genetic code, DeBenedictis and her colleagues had to modify some of life's most fundamental biochemistry. A cell's genetic information is first transcribed into messenger RNA. The ribosomes read the codons in the mRNAs and match them with the tRNAs in the transfer RNA. The ribosomes link the amino acids into a growing chain. Once the job is done, the mRNAs are degraded for recycling and the spent tRNAs are reloaded with amino acids.

The researchers made the Escherichia colibacteria have quadruplet anti-codons. The cells were tested to see if they could translate a quadruplet code, and if it would cause toxic effects or fitness defects. They found that all of the modified tRNAs could bind to quadruplet codons.

Nine out of 20 of the quadruplet anticodons were only recognized by the synthetases. A lot and a little of the nine amino acids can be translated with a quadruplet codon.