Mutation

A mutation is a heritable change in the genetic material of an organism. In many organisms, mutations can occur in germline cells, which are passed to offspring, or in somatic cells, which affect only the individual. Mutations can involve a single nucleotide change, small insertions or deletions, or larger changes such as duplications, inversions, or translocations. Mutations can also arise in mitochondrial DNA.

Mutations arise from errors during DNA replication, spontaneous chemical changes, or exposure to mutagens such as certain chemicals or ionizing radiation. Mechanisms include base substitutions (missense, nonsense, or silent), insertions and deletions that shift the reading frame, and larger chromosomal rearrangements. The cell employs repair systems—proofreading, mismatch repair, base excision repair, nucleotide excision repair, and double-strand break repair—to correct errors, but imperfect repair can introduce or fix mutations.

Effects of mutations vary with context. Many are neutral and have no observable effect; others are deleterious and can contribute to disease, while a minority are beneficial and can provide material for evolution. In populations, mutations generate new alleles and, together with recombination and natural selection, drive genetic diversity. Mutation rates differ among organisms, tissues, and environmental conditions.

Examples illustrate the range of mutation effects. A missense mutation in the beta-globin gene can cause sickle cell disease, while mutations in CFTR can underlie cystic fibrosis. Somatic mutations can contribute to cancer. In evolution, mutation supplies novel variation upon which other evolutionary forces act. Detection relies on DNA sequencing and genetic analysis, and ethical discussions surround human genome editing of germline mutations.