A mutation is any change in a DNA sequence. Point mutations substitute one nucleotide for another; they can be missense (different amino acid), nonsense (premature stop codon), or silent (same amino acid due to degeneracy). Frameshift mutations result from insertions or deletions that shift the reading frame, altering every codon downstream. Mutations can be caused by errors in DNA replication, errors in repair mechanisms, or external mutagens such as UV radiation or reactive chemicals. Errors in mitosis or meiosis can produce chromosomal changes: nondisjunction leads to aneuploidy (abnormal chromosome number), and structural changes include deletions, duplications, inversions, and translocations. Prokaryotes increase genetic variation through horizontal gene transfer via transformation, transduction, conjugation, and transposition. Mutations are the ultimate source of genetic variation for natural selection.
Why does a frameshift mutation typically have a more severe effect on protein function than a single missense mutation?