Gene Changes Previously Thought as Neutral Are Now Shown to Be Deleterious in Yeast

The early 1960s saw the crack of the genetic code. This scientific breakthrough brought advancement in biological and cellular studies. The underlying feature of the genetic code explains how DNA converts into protein. Codons are three-letter units found in DNA orders. Within these codons are the 20 amino acids that make up proteins in the human body. Mutations occur in gene codes as a letter or point change.

Genes

Genes

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There are two common types of these mutations. Silent mutations are changes in different parts of the DNA that don’t affect the protein order produced. Non-silent (non-synonymous) mutations cause changes in the protein order.

Previously held scientific beliefs have been that these silent mutations are neutral. However, a new study has demonstrated these silent changes are dangerous. This study is available in the journal Nature.

Presence of significant negative effect of the point mutation in a new study

Various studies have attempted to clarify the role of mutations in gene expression and diseases. The DNA sequence in proteins contains point changes that are silent in several cases. The sequencing of protein is unaffected by the changes. The point mutations are changes that do not affect protein sequence and are thought to be neutral since the 1960s. Researchers conducted experimental studies on the mechanisms of yeast gene engineering. The study result shows a high negative impact of silent gene changes (75.9%).

The results of this current study have a wide-ranging effect. In checking diseased mutations, scientists can recognize the role of both silent and non-silent mutations. The research in this innovative investigation also aimed to identify exceptions to the non-neutrality of silent mutations. Although some scientists believe that silent mutations are not neutral, there has not been much literature on the non-neutral exceptions.

The study subject was yeast. Since yeast has a short growth time and is tiny, the scientists checked the impact of these silent mutations on the organism fairly rapidly, accurately, and easily.

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The study scientists used CRISPR/Cas9 genome editing to determine more than 8000 mutant yeast sequences. Each of the sequences contained either a silent, non-silent, or nonsense mutation. Although 1.3% of the silent mutations discovered were highly advantageous, 75.9% were detrimental.

Additionally, the study investigated other mechanisms by which these silent changes affected Darwinian fitness. They discovered that both silent and non-silent mutations affect the gene expression level and the magnitude of these expressional changes shows the fitness effect.

Clinical significance

This study is significant in disease study and evolution biology. Because these silent mutations are harmful in yeast, clinicians and researchers can re-examine their previously held belief of its non-deleterious effects. This is significant because these silent mutations are now equally important in the pathogenesis of diseases.

Conclusion

The current study shows severe negative impacts of these silent mutations in yeast. Decades of consensus on the neutrality of silent gene changes may now be proven false. Understanding the mechanism of these changes can be beneficial for gene expression studies.

Read Also: Scientists Identify Gene Complex That Regulates Ribosome Production

References

Synonymous mutations in representative yeast genes are mostly strongly non-neutral

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