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Silent Genetic Mutations are Harmful

Marshall Nirenberg, a University of Michigan alumni, and a group of other scientists discovered the Genetic code of life in the early 1960s, identifying the mechanisms by which information in DNA molecules is translated into proteins, the live cell’s functioning components. They discovered codons, three-letter units in DNA sequences that dictate each of the 20 amino acids that make up proteins, work for which Nirenberg received a Nobel Prize with two other researchers.

Point mutations are single-letter misspellings in the Genetic code that occur on occasion. Nonsynonymous mutations affect protein sequences, whereas silent or synonymous mutations do not. In protein-coding DNA sequences, between one-quarter and one-third of point mutations are synonymous. Since the Genetic code was broken, those mutations have been thought to be neutral or virtually neutral.

However, University of Michigan scientists reveal that most synonymous mutations are severely damaging in work set for online publication in the journal Nature on June 8 that entailed Genetic manipulation of yeast cells in the lab. According to the study authors, the high non-neutrality of most synonymous mutations would have major ramifications for studying human disease processes, population and conservation biology, and evolutionary biology if proved true for additional genes and animals.

Simultaneous mutations had been assumed to be harmless since the Genetic code was cracked in the 1960s. “We have now demonstrated that this idea is incorrect,” study senior author Jianzhi “George” remarked “Zhang is the Marshall W. Nirenberg Collegiate Professor of Ecology and Evolutionary Biology at the University of Michigan.”Because many biological results are based on the assumption that synonymous mutations are neutral, its denial has far-reaching consequences. For example, synonymous mutations are frequently overlooked in the investigation of disease-causing mutations, despite the fact that they may represent a prevalent and underestimated mechanism.”

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