Most silent genetic mutations are harmful, not neutral, a finding with broad implications

Most silent genetic mutations are harmful, not neutral, a finding with broad implications

2022-06-08

In the early 1960s, University of Michigan alumnus Marshall Nirenberg and a few other scientists deciphered the genetic code of life, determining the rules by which information in DNA molecules is translated into proteins, the working parts of living cells.

They identified three-letter units in DNA sequences, known as codons, that specify each of the 20 amino acids that make up proteins, work for which Nirenberg later shared a Nobel Prize with two others.

Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Point mutations that alter the resulting protein sequences are called nonsynonymous mutations, while those that do not alter protein sequences are called silent or synonymous mutations.

Between one-quarter and one-third of point mutations in protein-coding DNA sequences are synonymous. Ever since the genetic code was cracked, those mutations have generally been assumed to be neutral, or nearly so.

But in a study scheduled for online publication June 8 in the journal Nature that involved the genetic manipulation of yeast cells in the laboratory, University of Michigan biologists show that most synonymous mutations are strongly harmful.

The strong nonneutrality of most synonymous mutations — if found to be true for other genes and in other organisms — would have major implications for the study of human disease mechanisms, population and conservation biology, and evolutionary biology, according to the study authors.

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