Mutation

A mutation is a change in the nucleic acid sequence of an organism's genome, which can occur in viruses or extrachromosomal DNA as well. These changes arise from mistakes made during DNA replication, mitosis, or meiosis, or from damage to DNA that leads to error-prone repair or replication errors like translesion synthesis. Mutations can also happen through the substitution, insertion, or deletion of DNA segments caused by mobile genetic elements. They may or may not lead to detectable changes in an organism's observable traits, or phenotype. Mutations are involved in both normal and abnormal biological processes, such as evolution, cancer, and the development of the immune system—including junctional diversity. Ultimately, mutation is the source of all genetic variation, supplying the raw material that natural selection and other evolutionary forces act upon.

Mutations can produce various types of sequence changes. In genes, they may have no effect, alter the gene's product, or prevent the gene from working properly or at all. Mutations can also occur in non-genic regions. A 2007 study of genetic variations among different Drosophila species suggested that when a mutation changes a protein produced by a gene, the result is likely harmful—about 70% of amino acid polymorphisms are estimated to be damaging, while the rest are neutral or marginally beneficial.

Mutation and DNA damage are the two main types of errors in DNA, but they are fundamentally different. DNA damage is a physical alteration in DNA structure, such as a single- or double-strand break, a modified guanosine residue like 8-hydroxydeoxyguanosine, or a polycyclic aromatic hydrocarbon adduct. Enzymes can recognize DNA damage and often repair it correctly using the complementary undamaged strand as a template, or an undamaged sequence from a homologous chromosome if available. If DNA damage remains in a cell, it may block gene transcription and thus protein translation, or it may block DNA replication and cause cell death. In contrast, a mutation is a change in the base sequence of DNA. Once the base change is present in both DNA strands, enzymes typically cannot recognize it, so mutations are not ordinarily repaired. At the cellular level, mutations can alter protein function and regulation. Unlike DNA damage, mutations are replicated when the cell divides. At the level of cell populations, cells with mutations increase or decrease in frequency based on how the mutations affect the cell's ability to survive and reproduce. Though distinct, DNA damage and mutations are related because DNA damage often causes errors during DNA synthesis in replication or repair, and these errors are a major source of mutations.

Mutations can involve duplicating large sections of DNA, often through genetic recombination. Such duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years. Most genes belong to larger gene families with shared ancestry, detectable by sequence homology. Novel genes arise through several methods, commonly by duplicating and mutating an ancestral gene, or by recombining parts of different genes to form new combinations with new functions. Protein domains act as modules, each with a specific, independent function, and can be mixed to produce genes encoding new proteins with novel properties. For instance, the human eye uses four genes to sense light—three for cone cell (color vision) and one for rod cell (night vision)—all derived from a single ancestral gene. Duplicating a gene (or an entire genome) also increases engineering redundancy, allowing one copy to acquire a new function while the other retains the original. Other mutation types occasionally create new genes from previously noncoding DNA.

Changes in chromosome number can involve even larger mutations, where DNA segments within chromosomes break and rearrange. For example, in Homininae, two chromosomes fused to form human chromosome 2; this fusion did not occur in other apes, which retain separate chromosomes. In evolution, such chromosomal rearrangements may primarily accelerate population divergence into new species by reducing interbreeding, thus preserving genetic differences between populations.

Sequences of DNA that can move around the genome, like transposons, make up a major fraction of plant and animal genetic material and may have been important in genome evolution. For instance, over a million copies of the Alu sequence exist in the human genome, and these sequences have been recruited to perform functions such as regulating gene expression. When these mobile DNA sequences move within a genome, they can mutate or delete existing genes, generating genetic diversity.

Nonlethal mutations accumulate in the gene pool, increasing genetic variation. Natural selection can reduce the abundance of some genetic changes, while other, more favorable mutations may accumulate and lead to adaptive changes. For example, a butterfly may produce offspring with new mutations. Most of these mutations will have no effect, but one might change the color of a butterfly's offspring, making it harder or easier for predators to see. If this color change is advantageous, the butterfly's chances of surviving and reproducing increase.