= Mutation
{wiki}
A mutation changes inherited genetic sequence. Under an <infinite sites mutation model>, every mutation occurs at a previously unmutated position, so mutations below the sample's common ancestor correspond to <segregating sites>.
More precisely, a <mutation> changes a genetic <nucleotide sequence>; in cellular <organisms> this is a <DNA> sequence. An altered sequence can be copied by <DNA replication> into descendant <biological cells>, changing their <genotype> whether or not an observable <phenotype> changes. Inheritance along a <cell lineage> does not require transmission to an offspring <organism>. In animals, <germline mutations> can enter offspring through <gametes>, whereas <somatic mutations> remain in body-cell lineages.<Mutation by National Human Genome Research Institute>[Definition and Narration: DNA sequence change, germline transmission and descendants of somatic cells]{ref}
A <DNA lesion> is damage to the physical <DNA> molecule, such as a damaged <nucleobase> or a broken strand. It need not become a lasting <mutation>: <DNA repair> can restore the original sequence. Conversely, a copied <nucleotide substitution> can leave an ordinary, correctly paired <DNA> duplex whose sequence differs from the ancestor. The distinction is between a damaged template and a changed inherited message, not simply between harmful and harmless effects.<Molecular Biology of the Cell, 4th edition by Bruce Alberts and others>[Chapter 5, DNA Repair, Without DNA Repair, Spontaneous DNA Damage Would Rapidly Change DNA Sequences; Figures 5-46–5-49]{ref}
Small <mutations> include <nucleotide substitutions> and <indels>. Larger changes can remove a <gene>, duplicate a <chromosome> region or rearrange its order. <Genetic recombination> can bring existing <alleles> together without creating a new <nucleobase> at the exchanged positions; the mechanism and the resulting sequence change are different questions. A molecular description of a <mutation>, its effect on a <gene> product and its effect on a <phenotype> are likewise three separate statements.
For an original consequence ledger, choose the <coding strand> segment $5'\text{-}\mathrm{ATG\ TTT\ GAA\ TAA}\text{-}3'$ with initiation at the first displayed <codon>. Use the standard <genetic code>, the same <reading frame> and suitable <gene expression> context throughout. Its <messenger RNA> has U in place of T, and the predicted <amino acid> chain is <methionine>–<phenylalanine>–<glutamic acid residue>, followed by a <stop codon>. This is a constructed coding segment, not an experimentally measured <gene>.
\Image[/mutation-sequence-consequence-ledger.png]
{title=Original <mutation> ledger: sequence changes and predicted coding consequences}
{description=All <DNA> segments are written $5'$ to $3'$ in the same chosen <reading frame>. Colored letters mark changed or inserted <nucleotides>; a gap marks a removed <codon>. Products follow the standard <genetic code> under the stated initiation assumption. The ledger predicts <amino acid> order or termination, not a measured <phenotype>.}
In the second row, position 6 changes from T to C, replacing TTT by TTC. Both corresponding <RNA> <codons> specify <phenylalanine>, so the predicted chain is unchanged. Changing position 5 from T to C instead gives TCT, whose <RNA> <codon> specifies <serine>. Changing position 7 from G to T gives TAA and therefore a <stop codon> before the original <glutamic acid residue>. Each is one <nucleotide substitution>, but their coding consequences differ. Even preservation of the <amino acid> chain does not guarantee unchanged <gene expression> or <phenotype>.
Insert GGA after ATG to add a <glycine> <codon>, or remove the complete TTT <codon> to remove <phenylalanine>. Both <indels> preserve the downstream <reading frame> because their lengths are three <nucleotides>. A one-<nucleotide> insertion at that location instead produces a <frameshift mutation>; the positional explanation and a worked regrouping appear under <frameshift mutation>. The ledger illustrates why interpreting a <genetic variant> requires its position and context, rather than just the label mutation.
<Mutation> supplies new inherited variation on which <natural selection> can act. The <Luria-Delbrück experiment> makes the distinction unusually visible: <natural selection> reveals resistant descendants, while the timing of a prior <mutation> determines how many descendants are available to reveal. This connects an invisible change in one <biological cell> to a visible pattern across <cell cultures>.
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