Abstract The approximate clocklike nature of the accumulation of nucleotide substitutions (the ‘molecular clock’) allows for the estimation of the time of divergence between modern species, dependent on calibrating the clock with known divergence dates from the fossil record. The use of fossils to calibrate divergence dates must be done thoughtfully, with an understanding that in most cases fossils provide a constraint on the minimal age of, rather than a true estimate of, the species divergence. Although older studies relied on single loci, recent publications have used complete genome sequences to estimate divergence. Although still dependent on assumptions of the model used, most recent estimates using the molecular clock give dates of approximately 5–8 million years ago for the human–chimpanzee divergence, in general agreement with the palaeontological evidence. Key Concepts: The molecular clock hypothesis proposes that nucleotide changes occur at a regular rate during evolution. Applying the molecular clock to sequence divergence among living species can provide an estimate of the time of the divergence of these species. The conversion from sequence divergence to units of geologic time usually requires calibration from the fossil record, although fossil‐free estimates have also been used. The first appearance in the fossil record of a given lineage provides a minimum age of divergence of taxa that created that lineage, not a point estimate of the divergence. Confidence in the fossil calibration is dependent on the completeness of the fossil record. Estimates of the human–chimpanzee divergence using the molecular clock have ranged from less than 3 million to nearly 12 million years ago (Ma). Most reliable estimates of the human–chimpanzee divergence range from 5 to 8 Ma. Considering the various sources of uncertainty associated with molecular dating, in general the dates are in agreement with palaeontological data.

The genetic divergence time between two species varies substantially across the genome, conveying important information about the timing and process of speciation. Here we develop a framework for studying this variation and apply it to about 20 million base pairs of aligned sequence from humans, chimpanzees, gorillas and more distantly related primates. Human-chimpanzee genetic divergence varies from less than 84% to more than 147% of the average, a range of more than 4 million years. Our analysis also shows that human-chimpanzee speciation occurred less than 6.3 million years ago and probably more recently, conflicting with some interpretations of ancient fossils. Most strikingly, chromosome X shows an extremely young genetic divergence time, close to the genome minimum along nearly its entire length. These unexpected features would be explained if the human and chimpanzee lineages initially diverged, then later exchanged genes before separating permanently.