MBE Advance Access published online on April 6, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi145
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1 Henry Wellcome Ancient Biomolecules Centre, Department of Zoology, University of Oxford, Oxford, United Kingdom
* To whom correspondence should be addressed. Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the higher, short-term (<1-2 Ma) mutation rate and the lower, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian proteincoding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration, but we cannot rule out the possibility that it is a spurious result arising from sequence errors. However, it is unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222 - 705 ka), Neandertals (108 ka; 70 - 156 ka), and modern humans (76 ka; 47 - 110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary time scales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.
Accepted March 31, 2005
Research Article
Time Dependency of Molecular Rate Estimates and Systematic Overestimation of Recent Divergence Times
2 Henry Wellcome Ancient Biomolecules Centre, Department of Zoology, University of Oxford, Oxford, United Kingdom; Present address: School of Environmental Sciences, University of Adelaide, Adelaide, Australia
3 Evolutionary Biology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom
Simon Y.W. Ho, E-mail: simon.ho{at}zoo.ox.ac.uk
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