DNA Sequences Decoded: Researchers Reveal the Harm 'Silent' Genetic Mutations May Bring

In a recently published study involving laboratory yeast cell manipulation, biologists at the University of Michigan showed that most synonymous mutations are strongly harmful.

As specified in a EurekAlert! report, in the early 1960s, Marshall Nirenberg, an alumnus at the said university, and a few other scientists translated the genetic code of life, identifying the rules by which "information in the molecules" is translated into the living cells' working parts known as proteins.

They were able to identify three-letter units in DNA sequences called "codons" that define each of the 20 amino acids that comprise proteins, work which Nirenberg shared a Nobel Prize with two others later.

Occasionally, single-letter misspellings in the genetic code called point mutations took place. Essentially, point mutations that change the resulting protein sequences are also known as nonsynonymous mutations. Those that don't change protein sequence, on the other hand, are called synonymous or silent mutations.

Synonymous Mutations

In the study published in the Nature journal, the researchers reported that 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 been genetically assumed to be neutral, or nearly so.

Most synonymous mutations' strong non-neutrality, if bound to be true for other genes and in other organisms, would have major implications for the research on human disease mechanism, population, conservation biology, and evolutionary biology, the study authors explained.

According to Jianzhi "George" Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology, since the genetic code was solved during the 1960s, synonym mutations have been generally believed to be benign. The professor added they now show that "this belief was false."

He also explained that since many biological conclusions depend on the presumption that synonymous mutations are neutral, its invalidation has expansive implications.

Nonneutral Mutations

For instance, as specified in the University of Michigan report, synonymous mutations are generally ignored in the stud of mutations that cause diseases, although they might be underappreciated, not to mention a common mechanism.

In recent decades, anecdotal evidence has suggested that certain synonymous mutations are nonneutral. Zhang and his colleagues wanted to find out if such cases are exceptions to the rule.

They opted to solve the issue in budding yeast since the short generation time of the organism of about 80 minutes and its tiny size enabled them to measure the impacts of a large number of synonymous mutations somewhat fast, accurately, and conveniently.

Use of CRISPR/Cas9 Genome Editing

The researchers used CRISPR/Cas9 genome editing to develop over 8,000 mutant yeast strains, each carrying a synonymous, nonsynonymous, or nonsense mutation in one of 21 genes they targeted.

Then, they measured each mutant strain by gauging how fast it reproduced relative to the nonmutant strain.

In a simple explanation, Darwinian fitness refers to the number of an individual's offspring. In this circumstance, measuring the yeast strains' reproduction rates showed if the mutations were beneficial, hazardous, or neutral.

To their surprise, the study investigators discovered that 75.9 percent of synonymous mutations were substantially deleterious, while 1.3 percent were substantially beneficial.

Related information about mutations and their types is shown on Don't Memorise's YouTube video below:

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