Silent Mutations Are Not Always Silent
“Mutations leading to identical amino acid sequences can change protein folding and function”… 12/21/06
Silent Mutations Speak Up
“Biologists have realized that the genetic code harbours a layer of information that they have largely ignored. Again.” 12/21/06
A mutation in a human gene that does not change the resulting amino acid can nevertheless change a protein’s function, according to an online report from Science. The research marks the first time that the phenomenon has been confirmed in mammals.
This time, the focus is on ‘silent’ mutations, single letter changes that were, as their name suggests, generally thought to have little impact on that gene’s instructions for making protein.
But a study published in Science this week shows that two silent mutations are nothing of the sort1. They seem to change the rate at which a drug-pumping protein folds and may help decide whether certain cancers become drug resistant.
Silent Ã¢â‚¬â€ also called synonymous Ã¢â‚¬â€ mutations arise because of the rules of the genetic code. Three chemical letters of DNA, called a codon, instruct the cell to insert a particular amino acid into the string that makes up a protein. But often several different codons code for the same amino acid.
A silent mutation is one that changes the triplet, but leaves the amino acid unchanged. “We were all educated that silent mutations should be ignored, and people really don’t pay attention to them,” says Chava Kimchi-Sarfaty at the National Cancer Institute in Bethesda, Maryland. But it is becoming clear that proteins made of identical amino acids can nevertheless behave differently.
It should be noted that synonymous (silent) mutations are an important part of the neutral theory of molecular evolution and are also an important part of molecular clock theory. If silent mutations are not so silent this handily explains why molecular clocks are such inconsistent timepieces.
One possible explanation is that ribosomes process codons at different rates when the codons differ only by a redundant nucleotide replacement. Think of the ribosome like a caulk gun producing a bead consisting of amino acid polymers that fold as they come out of the gun. If the rate at which the bead comes out changes then the shape it folds into changes as well. Another possibility is post-processing of the protein product where RNA molecules dependent on specific gene sequences alter the way the protein is processed after the ribosome finishes producing it.
Whatever the mechanism it really makes hash out of neutral theory and molecular clock theory.
Also note I’ve blogged in the past about how a design theoretic view predicts things like this. In this comment I described how the NTSC video signal evolved as intelligent designers added additional ways of encoding information to the carrier without effecting the preexisting ways and said we should look for DNA to have multiple encoding schemes one atop the other.