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

How very diverse what life is like on Earth, whether it’s a jaguar hunting a deer in the Amazon, an orchid spiraling around a tree in the Congo, primitive cells growing in boiling hot springs in Canada, or a stockbroker drinking coffee on Wall Street, at the genetic level, everything follows the same rules. Four chemical letters, or nucleotide bases, count 64 “words” of three letters called codons, each representing one of the 20 amino acids. When amino acids bind following these coded instructions, they form the characteristic proteins of each species. With only a few dark exceptions, all genomes encode information identically.

However, in a new study published last month in eLife, a group of researchers at the Massachusetts Institute of Technology and Yale University have shown that it is possible to modify one of these established rules and create a broader, completely new genetic code built around longer codonic words. In principle, his discovery points to one of several ways to expand the genetic code into a more versatile system that synthetic biologists could use to create cells with new biochemicals that make proteins found nowhere in nature. But the work also showed that an extended genetic code is hampered by its own complexity, becoming less efficient and even surprisingly less capable in some way, limitations that indicate why life may not have favored codons anymore. long in the first place.

It is unclear what these findings mean for how life could be coded elsewhere in the universe, but it implies that our own genetic code evolved to be neither too complicated nor too restrictive, but correct, and then ruled the life for billions of years later like what Francis Crick called a “frozen accident.” Nature chose this code of gold bars, the authors say, because it was simple and sufficient for its purposes, not because other codes were unattainable.

For example, with four-letter codons (quadruplets), there are 256 unique possibilities, not just 64, that may seem advantageous to life because it would open up opportunities to encode well over 20 amino acids and an astronomically more diverse variety of proteins. Previous studies of synthetic biology, and even some of these rare exceptions in nature, have shown that it is sometimes possible to increase the genetic code with a few quadruple codons, but so far no one has ever considered creating a completely quadruple genetic system to see how it works. compared to the normal triplet codon.

“This was a study that asked this question quite genuinely,” said Erika Alden DeBenedictis, lead author of the new article, who was a doctoral student at MIT during the project and is currently a postdoctoral fellow at the University of Washington.

Expansion of nature

To test a quadruple codon genetic code, DeBenedictis and his colleagues had to modify some of life’s most fundamental biochemicals. When a cell makes proteins, the first fragments of its genetic information are transcribed into messenger RNA (mRNA) molecules. Organelles called ribosomes read the codons of these mRNAs and bind them together with the complementary “anticodons” of the transfer RNA (tRNA) molecules, each of which carries a uniquely specified amino acid in its tail. Ribosomes bind amino acids in a growing chain that eventually folds into a functional protein. Once their work is completed and the protein is translated, the mRNAs are degraded for recycling and the spent tRNAs are reloaded with amino acids by enzyme synthetases.

The researchers modified the tRNAs Escherichia coli bacteria have quadruple anticodons. After subduing the genes of the E. coli in several mutations, they tested whether cells could successfully translate a quadruplet code and whether that translation would cause toxic effects or defects in fitness. They found that all modified tRNAs could bind to quadruple codons, which showed that “there is nothing biophysically wrong with translating to this larger codon size,” DeBenedictis said.

But they also found that the synthetases only recognized nine out of 20 of the quadruple anticodons, so they were unable to reload the rest with new amino acids. Having nine amino acids that can be translated with a quadruple codon to some extent is “a lot and a little bit,” DeBenedictis said. “It’s a lot of amino acids for something that nature never needs to work.” But it’s partly because the inability to translate 11 essential amino acids strictly limits the chemical vocabulary life has to play with.

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