Disproving A 60-Year-Old Hypothesis: Most “Silent” Mutations Are Actually Harmful

An Anonymous Coward writes:

A new study finds that most "silent" mutations are harmful rather than neutral:

Marshall Nirenberg, a University of Michigan alumni, and a small group of researchers cracked the genetic code of life in the early 1960s, figuring out the rule by which information stored in DNA molecules is converted into proteins, the functional components of living cells.

They discovered three-letter DNA units called codons that describe each of the 20 amino acids that make up proteins. This discovery would win Nirenberg and two others the Nobel Prize.

Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Nonsynonymous mutations are point modifications that alter the protein sequences that result from them, while silent or synonymous mutations do not change the protein sequences.

[...] Since the genetic code was solved in the 1960s, synonymous mutations have been generally thought to be benign. We now show that this belief is false," said study senior author Jianzhi George" Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology.

Because many biological conclusions rely on the presumption that synonymous mutations are neutral, its invalidation has broad implications. For example, synonymous mutations are generally ignored in the study of disease-causing mutations, but they might be an underappreciated and common mechanism."

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