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Ars Technica AI·Research·1d ago·by John Timmer·~2 min read

Researchers try to cut the genetic code from 20 to 19 amino acids

Researchers try to cut the genetic code from 20 to 19 amino acids

The genetic code is central to life. With minor variations, everything uses the same sets of three DNA bases to encode the same 20 amino acids. We have discovered no major exceptions to this, leading researchers to conclude that this code probably dated back to the last common ancestor of all life on Earth. But there has been a lot of informed speculation about how that genetic code initially evolved.

Most hypotheses suggest that earlier forms of life had partial genetic codes and used fewer than 20 amino acids. To test these hypotheses, a team from Columbia and Harvard decided to see if they could get rid of one of the 20 currently in use. And, as a first attempt, they engineered a portion of the ribosome that worked without using an otherwise essential amino acid: isoleucine.

Changing the code

First off, why would you do this? Most work in the field has focused on altering the genetic code in ways that are useful, such as using more than 20 amino acids to enable interesting chemistry.

The reasoning here seems to be that, prior to the last common ancestor of life on Earth, organisms experimented with various genetic codes and probably used a mix of proteins and catalytic RNAs to run their metabolisms. While we’ve done a lot of studies on catalytic RNAs, we have far less of an idea of what sort of chemistry is possible with a reduced genetic code. And the researchers suggest that AI-based tools have matured enough that redesigning proteins to use fewer amino acids is far more realistic than it was just a few years ago.

Isoleucine is one of three highly similar amino acids, along with leucine and valine. In the portion of the structure that’s distinct from other amino acids, all three have a branched structure that’s composed entirely of carbon and hydrogen. That makes them all hydrophobic, and they often are located in the interior of proteins, which keeps them away from the watery environment of the cell. So, purely by reasoning it out, one of those three would seem to be a good candidate to get rid of.

Researchers try to cut the genetic code from 20 to 19 amino acids — image 2
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