Researchers Aim to Shrink Genetic Code From 20 to 19 Amino Acids
▼ Summary
– The genetic code is nearly universal, using the same three-DNA-base sets to encode 20 amino acids, and likely dates back to life’s last common ancestor.
– Researchers are testing hypotheses that early life used partial genetic codes with fewer amino acids by engineering the ribosome to function without isoleucine.
– Most work on altering the genetic code aims to expand it beyond 20 amino acids for useful chemistry, such as enabling new reactions.
– This study explores what chemistry is possible with a reduced genetic code, a gap in knowledge compared to extensive studies on catalytic RNAs.
– Isoleucine was chosen for removal because it is one of three similar hydrophobic amino acids (with leucine and valine) that are structurally and chemically redundant.
The blueprint of life, encoded in our genetic code, has remained remarkably consistent across nearly all organisms. With only minor variations, every living thing uses the same triplet DNA sequences to produce the same 20 essential amino acids. This universal system is so ancient that scientists believe it dates back to the last universal common ancestor of all life. But how did this code first emerge? That question has fueled decades of informed debate.
Most theories propose that early life forms operated with a partial genetic code, relying on fewer than 20 amino acids. To put this hypothesis to the test, a collaborative team from Columbia and Harvard set out to see if they could eliminate one of the 20 amino acids currently in use. Their first target was isoleucine, an amino acid they successfully removed from a key portion of the ribosome, proving the concept is viable.
Why would anyone want to shrink the genetic code? Much of the existing research has focused on expanding it, adding new amino acids to enable novel chemical reactions. The logic behind this reductionist approach is different. Before the last common ancestor, early life likely experimented with various codes, possibly relying on a mix of proteins and catalytic RNAs. While we have extensively studied catalytic RNAs, we know far less about the chemistry possible with a reduced amino acid set. The researchers argue that modern AI-based protein design tools have matured enough to make this sort of engineering far more realistic than it was just a few years ago.
Isoleucine is one of three structurally similar amino acids, alongside leucine and valine. All three share a branched, carbon-and-hydrogen side chain that makes them hydrophobic. This property often places them in the interior of proteins, safely away from the cell’s watery environment. By simple logic, one of these three seemed like the best candidate to remove. The team’s success with isoleucine opens the door to a deeper understanding of how life’s fundamental building blocks evolved.
(Source: Ars Technica)
