  Observations that rates of molecular evolution vary widely within and among
lineages have cast doubts upon the existence of a single molecular clock.
Differences in the timing of evolutionary events estimated from genetic and
fossil evidence have raised further questions about the existence of molecular
clocks and their use. Here we present a model of nucleotide substitution that
combines new theory on metabolic rate with the now classic neutral theory of
molecular evolution. The model quantitatively predicts rate heterogeneity, and
reconciles differences in molecular- and fossil-estimated dates of evolutionary
events. Model predictions are supported by extensive data from mitochondrial
and nuclear genomes. By accounting for the effects of body size and temperature
on metabolic rate, a single molecular clock explains heterogeneity in rates of
nucleotide substitution in different genes, taxa, and thermal environments.
This model suggests that there is indeed a general molecular clock, as
originally proposed by Zuckerkandl and Pauling, but that it ticks at a constant
substitution rate per unit mass-specific metabolic energy rather than per unit
time. More generally, the model suggests that body size and temperature combine
to control the overall rate of evolution through their effects on metabolism.
