written by: Robyn Broyles•edited by: Paul Arnold•updated: 3/6/2017
Geneticists long dismissed certain mutations as "silent," believing them to have no effect. But a significant body of research has proved this assumption false. Many so-called silent mutations are actually harmful mutations that are proven to cause genetic diseases in humans.
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A silent mutation is one that does not change the amino acid sequence encoded by a gene. The name reflects the common-sense assumption that silent mutations have no effect on phenotype. But the process of synthesizing proteins from the information in DNA is more complicated than simply reading the code and translating it into an amino acid chain.
Researchers have discovered that in many cases, a silent mutation is not silent at all. Often, these simple changes may even be harmful mutations.
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Silent Mutations That Are Harmful in Humans
A point mutation that changes a codon to a synonym (one that codes for the same amino acid) is also known as a synonymous mutation. About 50 genetic diseases have been linked to synonymous mutations, proving that these codon switches can be harmful mutations in some circumstances. This includes silent mutations in CFTR, the gene that is linked with Cystic fibrosis.
Silent point mutations can change how the cell recognizes exons and introns. Exons are the useful, coding parts of a gene, while introns are non-coding "garbage" DNA found among the exons. Before a protein can be synthesized, the cell machinery must locate and remove the introns from the mRNA. Researchers have found that silent mutations can cause errors in the intron-seeking process, causing the protein to be translated incorrectly.
Another way a "silent" mutation can cause a problem is by affecting the mRNA's shape. Usually, mRNA folds into a particular shape due to interactions of its constituent bases. This shape affects the speed of translation as well as the rate at which the cellular machinery degrades it. A silent mutation can change the way mRNA folds, leading to the production of too much or too little of the encoded protein.
Geneticists hypothesize that changing the rate of translation can even affect protein folding, a complex but critical part of protein production. Some cancer researchers believe that this factor may cause a specific mutation that increases the resistance of cancer cells to chemotherapy drugs.
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Silent Mutations and tRNA
Humans are not the only creatures affected by not-so-silent mutations. In some organisms, synonymous mutations can affect gene expression. It turns out that many bacteria have unequal numbers of the different types of tRNA segments. A tRNA is necessary to match a codon and attach the correct amino acid to a polypeptide chain. If a synonymous mutation changes a codon from one with a large number of tRNAs to one with few tRNAs, even if they carry the same amino acid, protein production slows down. Also, some tRNAs bind more easily to some codons than to other (synonymous) codons, so a mutation to a poorer-binding synonymous codon increases the likelihood of a translation error.
Researchers have found these effects in some bacteria, yeasts, plants, and simple animals. For unknown reasons, these tRNA effects are not a factor for humans and other mammals.