Single mutations in genes long thought to be neutral are actually harmful to an organism’s fitness.
These “silent” mutations, known as synonymous mutations, are a single nucleotide change in genes that code for proteins. These mutations don’t ultimately alter the protein encoded by the gene.
About a quarter to a third of single mutations in protein-coding genes are synonymous, says Jianzhi “George” Zhang, a professor of ecology and evolutionary biology at the Univ. of Michigan. The rest are non-synonymous, meaning they do alter the coded-for protein. Most non-synonymous mutations are bad for organisms, but for decades, scientists have assumed that synonymous mutations had little to no effect.
The new research turns that notion on its head. The synonymous, “silent,” mutations are just as likely as non-synonymous mutations to stunt fitness, Zhang and his colleagues reported in the journal Nature. The findings will require a rethinking of experiments that use synonymous mutations as a control group when studying the damage from mutations that do alter proteins. They may also have implications for human disease.
“People ignore synonymous mutations when they look for disease mutations,” Zhang says. But there may be disease-causing genes among this understudied subset.
Already, there are scattered examples of synonymous mutations causing problems. Researchers reported in 2017 in the journal PLOS Biology that...
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