Neutral Evolution Rate Calculator
Calculate neutral substitution rate, synonymous site divergence, and test neutral theory.
The Molecular Clock and Why Divergence Is Doubled
Kimura's neutral theory holds that most substitutions that fix are selectively neutral, so they accumulate at the underlying mutation rate. That gives a clock — but the divergence between two sequences counts changes along both lineages since their common ancestor.
The factor of two is the commonest error in the calculation. Two species that split 10 million years ago have each accumulated substitutions for 10 million years, so the total path length is 20 million years of evolution.
| Sequence class | Approximate rate (per site per year) |
|---|---|
| Synonymous sites | ≈ 5 × 10−9 — near neutral |
| Pseudogenes | ≈ 5 × 10−9 |
| Non-synonymous sites | ≈ 1 × 10−9 — constrained |
| Histone genes | < 10−10 — extremely conserved |
The spread across that table is the evidence for the theory. Sites where changes have no phenotypic consequence evolve fastest; sites under functional constraint evolve slowest. Rate variation between classes reflects selection, not mutation.
Why the Clock Is Not Strictly Constant
| Factor | Effect on rate |
|---|---|
| Generation time | Shorter generations, faster clock per year |
| Metabolic rate | Higher rate, more oxidative damage |
| DNA repair efficiency | Varies between lineages |
| Effective population size | Affects fixation of nearly neutral variants |
The generation time effect is substantial: rodents accumulate substitutions per year several times faster than primates, because replication errors arise per generation rather than per year. This is why modern dating uses relaxed clock models that allow rates to vary across a phylogeny rather than assuming one global rate.
Saturation limits the method at long timescales. Once multiple substitutions have occurred at the same site, observed divergence underestimates true divergence, and correction models such as Jukes–Cantor or Kimura two-parameter become necessary.
Worked Examples
Common Mistakes
Divergence accumulates along both lineages since the common ancestor. Using T rather than 2T doubles the calculated rate.
Generation time and metabolic rate differ substantially. Rodents evolve several times faster per year than primates.
Multiple hits at the same site cause observed divergence to underestimate true divergence. Jukes–Cantor or similar correction is needed.
They are under selection and evolve more slowly and less regularly. Synonymous sites and pseudogenes approximate neutrality far better.