"Silent" mutations are not always silent

Mutations leading to identical amino acid sequences can change protein folding and function

Charles Q. Choi
Dec 20, 2006
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."The habit we all have of disregarding nucleotide changes that don't change protein sequence may not be a good one," coauthor Michael Gottesman at the National Cancer Institute in Bethesda, Md., told The Scientist. "This may be a generalizable phenomenon that may lead to changes in function we haven't been thinking about."Gottesman and his colleagues investigated MDR1, which encodes P-gp, a human membrane transport protein that helps cells pump out anticancer and other drugs. They focused on the C3435T, a single nucleotide polymorphism (SNP) that is synonymous or silent, encoding for the same amino acid as the gene's wild-type version.The researchers first used viral vectors against...