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Using the molecular clock to determine when lineages diverged requires that the neutral mutations accumulate at a constant rate. Which doesn't happen, for several reasons:

^ Differences between genes: There is no reason to think that the proportion of neutral mutations should be constant across genes with different functions. One protein may function only if it's exactly the right shape or configuration to do its job; another protein may do its job pretty well even in spite of a few changes. At the very least, comparisons should be made only between the same gene in different species. But even then, scientists can't be sure that a gene shared across two species performs the same function. The function of the gene may have changed as the species evolved to a different environment, for example.

^ Population size and generation time: The rate at which neutral mutations become fixed in a population is a function of population size and generation time, both of which may vary between lineages after they diverge. In small populations with short generation times, neutral mutations rise to fixation more rapidly.

^ Strength of selection: The strength of natural selection may vary between species over time, thus changing the ratio of neutral to nonneutral mutations that rise to fixation.

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