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 published online 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.
“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.
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