Point mutation

A point mutation affects a single base pair. Terminology varies: the broad usage includes a one-base pair insertion or deletion as well as a nucleotide substitution. Describing the actual sequence change avoids this ambiguity.^[ref]

A nucleotide substitution replaces a nucleotide at a specified position without changing sequence length. In a fixed reading frame, a single substitution can preserve an amino acid assignment, change it or introduce a stop codon; the mutation ledger exhibits all three possibilities.

An observed transition-transversion ratio compares the number of nucleotide transitions with the number of nucleotide transversions in a specified set of sequence alignment differences:Six transition differences and two transversion differences give $R=3$. If no transversion is observed, this ordinary finite ratio is undefined; the raw counts should remain explicit.

The instantaneous rate parameter can use a different convention. In the Kimura two-parameter model, let $\alpha$ be the rate to the one transition target and $\beta$ the rate to each of the two transversion targets from a base. ThenThus $\kappa =4$ corresponds to twice as many instantaneous transition events as total transversion events, not four times as many.^[ref]

Observed endpoint differences can hide repeated nucleotide substitutions. Under independent uniform endpoint bases, the four directed transition mismatches and eight transversion mismatches give a limiting ratio $1/2$, even when short-time event rates differ. Always state whether the ratio describes scored differences, total events or rates per possible target.

A nucleotide transversion is a nucleotide substitution from a purine-derived base to a pyrimidine-derived base, or the reverse. In DNA, the unordered pairs are $A\leftrightarrow C$, $A\leftrightarrow T$, $G\leftrightarrow C$ and $G\leftrightarrow T$. A nucleotide transition instead stays within one of these chemical classes.^[ref]

Each starting base has two possible transversion targets and one transition target. Thus twelve directed changes split into eight transversions and four transitions. Equal counts of possible events do not imply equal observed frequencies: chemical mutation mechanisms and natural selection can affect those frequencies.

Suppose an illustrative sequence alignment contains twelve transition differences and eight transversion differences. Its observed transition-transversion ratio is $12/8=1.5$. That ratio summarizes the scored differences; repeated substitutions at the same site can make it differ from the ratio of underlying instantaneous rates. The two-class distinction motivated the Kimura two-parameter model.^[ref]

A nucleotide transition is a nucleotide substitution between two purine-derived bases or between two pyrimidine-derived bases. In DNA, the possibilities are $A\leftrightarrow G$ and $C\leftrightarrow T$: adenine exchanges with guanine, or cytosine with thymine. The chemical class is preserved; the identity of the base changes.^[ref]

From any specified DNA base, there is exactly one possible transition target and two nucleotide transversion targets. If all three targets were equally likely, transitions would comprise $1/3$ of changes. This is a counting baseline, not a biological law about mutation rates. The Kimura two-parameter model allows the rates for these two classes to differ.^[ref]

The classification does not determine a mutation's effect on a protein. A transition can preserve an amino acid, change it or introduce a stop codon, depending on the affected codon.

The Jukes-Cantor model is a symmetric four-state continuous-time Markov chain for DNA evolution. Each change to a specified different base has rate $q$, so the total rate of actual changes is $3q$. Its same-base probability is $1/4+(3/4)e^{-4qt}$ and its probability for one specified different base is $(1/4)(1-e^{-4qt})$. The probability of any mismatch is three times the latter, tending to $3/4$ at long times. Distinguish the exponent parameter $4q$ from the actual per-site mutation rate $3q$ when fitting this model.