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 find 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. Normally, mRNA folds into a specific 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 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.