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
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.
One-quarter to one-third of protein-coding DNA sequence point mutations are synonymous. They have often been thought to be neutral or almost neutral mutations ever since the genetic code was deciphered.
But in a study recently published 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 non-neutrality 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.
“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.”
In the past decade, anecdotal evidence has suggested that some synonymous mutations are nonneutral. Zhang and his colleagues wanted to know if such cases are the exception or the rule.
They chose to address this question in budding yeast (Saccharomyces cerevisiae) because the organism’s short generation time (about 80 minutes) and small size allowed them to measure the effects of a large number of synonymous mutations…
Read More: Most “Silent” Mutations Are Actually Harmful