A missense mutation is an alteration in the DNA that results in a different amino acid being incorporated into the structure of a protein. At a molecular level, DNA is made up of two strands of four nucleotides called adenine, cytosine, guanine, and thymine (i.e., A, C, G, T, respectively). In order to produce a protein, DNA must first be transformed into messenger RNA, or mRNA, by an enzyme called RNA polymerase. This mRNA is then encoded so that any three nucleotides correspond to a specific codon, which codes for a specific amino acid, or is a stop codon, which indicates that protein synthesis is complete. In the final step of translation, specialized proteins called ribosomes use the mRNA molecule to read each codon and match them with the corresponding amino acids that will ultimately make up the final protein.
Missense mutations occur when a single nucleotide base in a DNA sequence is swapped for another one, resulting in a different codon and, therefore, a different amino acid. These mutations are quite common and, in most cases, they don’t affect the overall shape and function of the protein. However, when the amino acid substitution involves two amino acids with very different chemical properties, missense mutations can lead to significant changes in protein function. In such cases, they are known as non-conservative missense mutations.