How Do Mutations Affect Protein Structure?
Learn how DNA mutations can change amino acid sequences, protein folding and function, and why substitutions or changes in non-coding DNA may have no effect.
A mutation changes the DNA base sequence. If it occurs in a gene, it may change the sequence of amino acids in the protein made from that gene. This can alter how the protein folds and functions, but not every mutation changes a protein.
From DNA to protein
A gene’s base sequence is transcribed into messenger RNA (mRNA). At a ribosome, the mRNA is translated: each group of three bases, called a codon, specifies an amino acid. The order of amino acids is the protein’s primary structure. Bonds and interactions between parts of the chain then help it fold into its three-dimensional shape, including its tertiary structure.
A substitution replaces one DNA base with another. It might specify a different amino acid, which could change the protein’s folding. If the protein is an enzyme, a change to its active site may prevent its substrate from binding effectively. However, the genetic code is degenerate: more than one codon can specify the same amino acid, so a substitution can leave the protein unchanged.
An addition or deletion inserts or removes DNA bases. If the number of bases added or removed is not a multiple of three, it causes a frame shift: the bases are read in different groups from that point onwards. For example, inserting one base after the first triplet changes the grouping from ATG GAA TTT…\mathrm{ATG\ GAA\ TTT\ldots}ATG GAA TTT… to ATG CGA ATT T…\mathrm{ATG\ CGA\ ATT\ T\ldots}ATG CGA ATT T…. Several later amino acids may therefore change.
AQA also includes inversion, duplication and translocation as mutation types. Their effects depend on where the DNA change occurs. In an exam answer, avoid saying that every mutation changes an amino acid or makes a protein non-functional: the mutation may be in non-coding DNA, or the resulting protein may still work.
