Could life use a longer genetic code?Maybe, but unlikely

Various Like life on Earth – whether it’s a jaguar hunting deer in the Amazon, an orchid vine coiling a tree in the Congo, a primordial cell growing in a boiling hot spring in Canada, or sipping coffee stocks on Wall Street Brokers – At the genetic level, it all follows the same rules. Four chemical letters, or nucleotide bases, spell out 64 three-letter “words,” called codons, each representing one of 20 amino acids. When amino acids are strung together following these coded instructions, they form proteins that are unique to each species. With a few lesser-known exceptions, all genomes encode information in the same way.

However, in a new study published last month in Elef, a team of researchers at MIT and Yale University have shown that it is possible to tweak one of these time-honored rules and create a broader, entirely new genetic code around longer codon words. In principle, their findings point to one of several ways to expand the genetic code into a more general system that synthetic biologists can use to create cells with new biochemistry that makes proteins nowhere to be found in nature. . But the work also shows that the expanded genetic code, hampered by its own complexity, becomes in some ways less efficient and even unexpectedly less capable — constraints that hint at why life may not be favored in the first place longer codons.

It’s uncertain what these findings mean for how life elsewhere in the universe is encoded, but it does mean that our own genetic code evolved to be neither too complex nor too restrictive, and just right — and then dozens of times thereafter. Ruled life for 100 million years Francis Crick called it a “freeze accident.” The authors say that nature chose this Goldilocks code because it was simple and sufficient for its purpose, not because other codes could not.

For example, for a four-letter (quadruplet) codon, there are 256 unique possibilities instead of just 64, which seems to be good for life, as it would be useful for encoding a large number of more than 20 amino acids and more diverse Protein arrays offer opportunities. Previous Synthetic Biology Research, and even some rare exceptions in nature, showing that it is sometimes possible to augment the genetic code with several quadruplets of codons, but until now, no one has attempted to create a fully quadruplet genetic system to see how it compares to normal compared to genetic systems. Triple codon one.

“This study raises this question very sincerely,” said Erika Alden DeBenedictis, lead author of the new paper, who was a doctoral student at MIT during the project and is currently a postdoc at the University of Washington.

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To test the quadruplet genetic code, DeBenedictis and her colleagues had to modify some of life’s most fundamental biochemistry. When a cell makes a protein, fragments of its genetic information are first transcribed into messenger RNA (mRNA) molecules. Organelles called ribosomes then read the codons in these mRNAs and match them with complementary “anti-codons” in transfer RNA (tRNA) molecules, each with a unique tail amino acid. Ribosomes link amino acids into a growing chain that eventually folds into a functional protein. Once their work is done and the protein is translated, the mRNAs are degraded for recycling, and the spent tRNAs are reloaded with amino acids by synthetases.

Researchers tweaked tRNA to Escherichia coli Bacteria have quadruplex anticodons.After receiving the gene Escherichia coli Against various mutations, they tested whether cells could successfully translate the quadruplet, and whether this translation could lead to toxic effects or fitness defects. They found that all modified tRNAs could bind to quadruplet codons, suggesting that “translation with this larger codon size is not biophysically problematic,” DeBenedictis said.

But they also found that synthetases can only recognize 9 of the 20 quadruplet anticodons, so they couldn’t charge the remaining anticodons with new amino acids. There are nine amino acids that can be translated to some extent with quadruple codons, which is “both more and less,” DeBenedictis said. “That’s a lot of amino acids for things that nature doesn’t need to work on.” But that’s a bit because the inability to translate the 11 essential amino acids severely limits the chemical vocabulary that life must use.

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