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Mutation

The ultimate source of genetic variation

Try it: Two-Way MutationIrreversible

Mutation as an Evolutionary Force

Mutation is the only source of new genetic variation. Without mutation, evolution would eventually stop as selection and drift fix alleles. However, mutation alone is a weak evolutionary force — it takes many generations to appreciably change allele frequencies.

Key insight: Mutation provides the raw material for evolution. Selection, drift, and gene flow then shape how that variation changes over time.

Mutation Rates

The mutation rate (μ) is the probability that an allele mutates per generation. For most genes, rates are on the order of 10⁻⁴ to 10⁻⁸ per generation.

  • Point mutations: ~10⁻⁸ per base pair per generation
  • Gene-level mutations: ~10⁻⁵ to 10⁻⁶ per gene per generation
  • Structural variants: Higher rates, more variable

Two-Way Mutation Model

In the simplest model, mutations occur in both directions:

A →(μ) a and a →(ν) A Forward (μ) and back (ν) mutation

The change in allele frequency per generation is:

Δp = -μp + ν(1-p) Change due to bidirectional mutation

At equilibrium (Δp = 0):

p̂ = ν / (μ + ν) Mutation equilibrium frequency

Interactive Mutation Dynamics

Adjust mutation rates to see how allele frequencies change over time. Notice how slowly mutation changes frequencies compared to selection or drift.

0.00010
0.00002
Equilibrium p̂ 0.1667

Starting from p = 0.9, the population slowly approaches mutation equilibrium.

Time Scale of Mutation

Mutation is slow! The half-life for approaching equilibrium is:

t₁/₂ ≈ 0.693 / (μ + ν) Half-life of approach to equilibrium

With typical mutation rates (μ ≈ 10⁻⁵), this means tens of thousands of generations — far longer than most evolutionary changes we observe.

Irreversible Mutation

When back mutation is negligible (ν ≈ 0), the model simplifies:

p(t) = p₀ × e^(-μt) Exponential decay under irreversible mutation

The favored allele A declines exponentially toward loss. This applies when one allele mutates to many possible forms but the reverse is unlikely.

Mutation-Selection Balance

In reality, most mutations are deleterious. Selection removes them, but mutation keeps introducing them, creating a dynamic equilibrium:

q̂ ≈ μ/s (for recessive mutations) Equilibrium frequency of deleterious allele
q̂ ≈ μ/(hs) (for partially dominant mutations) When deleterious effects are partially dominant

This explains the genetic load — populations carry many slightly deleterious alleles at low frequencies.

Neutral Mutations

Most mutations that persist are neutral — they have no effect on fitness. Neutral theory (Kimura, 1968) shows that:

  • Rate of neutral substitution equals the mutation rate: k = μ
  • Most variation within populations is selectively neutral
  • Drift, not selection, determines the fate of neutral alleles
k = μ (substitution rate = mutation rate) Neutral theory prediction
The molecular clock arises from neutral theory: if substitutions occur at rate μ, sequence divergence between species reflects time since their common ancestor.

Mutation in Finite Populations

In real populations, new mutations start at frequency 1/(2N). Their fate depends on selection:

  • Neutral: Probability of fixation = 1/(2N)
  • Beneficial (s > 0): Probability ≈ 2s (when Ns >> 1)
  • Deleterious: Usually lost quickly

The expected number of new mutations entering a population per generation is:

2Nμ (new mutations per generation) Input of new variation

Types of Mutations

Point Mutations

  • Synonymous: No amino acid change (usually neutral)
  • Nonsynonymous: Amino acid change (variable effects)
  • Nonsense: Creates stop codon (usually deleterious)

Structural Mutations

  • Deletions/Insertions: Remove or add DNA
  • Duplications: Can create new gene copies
  • Inversions: Reverse segment orientation
  • Translocations: Move segments between chromosomes