An archaea can “tolerate uncertainty” and read the same codon in two different ways, calling into question a 60-year-old dogma. “It’s like adding another letter to the alphabet” of the genetic code, which now has 21 amino acids instead of the 20 we know.
Living organisms usually read the DNA code in a very rigid and predictable way. Each codonthe set of three nucleotides in a gene, corresponds to a specific amino acid that becomes part of a protein in formation.
Researchers at the University of California, Berkeley, have now discovered that a type of microorganism can tolerate uncertainty in this process.
The work, presented in a recently published in Proceedings of the National Academy of Sciences calls into question the idea, defended for decades, that the genetic code must be always interpreted with complete precision.
This microorganism, a methane producer belonging to the domain Archaeaprokaryotic microorganisms that are characterized by having a morphology similar to that of bacteria, but distinct molecular organization, read a certain sequence of three letters in two different ways.
Although the codon normally serves as a “stop” signal, ending protein production, the organism sometimes treats it as an indication to continue to build protein.
The result is the formation of two versions of the same proteinand the choice appears to be influenced, in part, by environmental conditions.
The species, Methanosarcina acetivoransremains healthy while operating with this flexible decoding system, showing that life can operate with a slightly imperfect genetic code.
Scientists think this ambiguity may have evolved to allow the organism add a rare amino acid, called pyrolysisan enzyme that helps it degrade methylamine, a common environmental compound, even detected in the human intestine.
Ambiguity as an advantage
“Objectively, the ambiguity in the genetic code should be destructive; would end up generating a random set of proteins”, says Dipti Nayakassistant professor of molecular and cellular biology at UC Berkeley and senior author of the paper.
“But biological systems are more ambiguous than we give them credit for, and this ambiguity is actually a feature — not a bug”, adds the researcher, cited by .
As archaea that “eat” methylaminesand the bacteria that may have acquired this ability, play an important role in the human organism.
In the liver, metabolites released by red meat are converted into trimethylamine N-oxide, a compound associated with cardiovascular disease. We depend on these microorganisms to remove methylamines before they reach the liver.
The findings have implications for future therapies. Some researchers had already suggested that introduce some inaccuracy ntranslation machinery could help address diseases caused by “stop codes” premature births in important genes, which lead to the production of non-functional proteins.
This includes about 10% of all genetic diseasessuch as cystic fibrosis or Duchenne muscular dystrophy. Making a stop “codon” a little “leaky” could allow the production of enough of the normal protein to alleviate symptoms.
The DNA of the genome is initially transcribed into RNA and this genetic code is then read by cellular machinery to produce proteins. The nucleic acids that make up RNA come in four variants — adenine (A), cytosine (C), guanine (G) and uracil (U).
In most organisms studied to date, groups of three nucleic acids, or codons, are attributed to a single amino acid or to a so-called “stop codon”, which ends the synthesis of that protein. When RNA is translated into a chain of amino acids, the machinery always respects this one-to-one association.
Not all organisms decode RNA in the same way. Some attribute a different amino acid at a given codonsome have more than the “standard” 20 amino acids per organism, and the codons are redundant — several can code for the same amino acid.
But uniformly throughout the tree of life, each codon has only one meaning — no exceptions. “It’s essentially like a cipher,” explains Nayak. “You are taking something in one language and translating it into anothernucleotides for amino acids.”
Scientists have long known that many members of the domain Archaea produce pyrrolysine, which gives them 21 amino acid optionsinstead of the usual 20, from which they can manufacture proteins. This brings advantagessays the hero.
“When we have a new amino acid, the world opens up“, adds the researcher. “We can start playing with a much larger code. It’s like add another letter to the alphabet”.
