Molecular clock

The molecular clock is the approximately constant rate at which neutral mutations accumulate in DNA and protein sequences over geological time, enabling estimation of divergence dates from sequence data. It follows directly from the Neutral Theory of Molecular Evolution: if most molecular substitutions are selectively neutral and fixed by drift, then the substitution rate is determined by the mutation rate, which is roughly constant per generation within a lineage. Calibrate the rate against fossil evidence at one divergence node, and you can date other divergence events from sequence divergence alone.

The clock is not perfectly regular. Generation time, metabolic rate, DNA repair efficiency, and effective population size all cause rate heterogeneity among lineages — the rate heterogeneity problem that requires statistical correction in modern molecular dating analyses. Bayesian relaxed-clock methods allow the clock to vary across branches while still extracting divergence estimates. These methods have transformed phylogenetics and are now standard in molecular dating.

The molecular clock should be understood as a useful approximation with known failure modes, not as a law of nature. Lineages under strong positive selection, or that have undergone dramatic changes in population size or generation time, will show clock violations that naive application of the method cannot handle. The appropriate response is to model the violations explicitly, not to treat the clock as a free parameter to be adjusted until it gives convenient dates. See also: Biological Evolution, Motoo Kimura, Rate Heterogeneity.