Bayesian Estimation of Substitution Rates from Ancient DNA Sequences with Low Information Content

Rates of molecular evolution have been shown to vary significantly among nucleotide sites, loci, and taxa. In addition to these forms of rate heterogeneity, there is evidence that molecular rates vary with the timescale over which they are estimated. One of the most striking observations has been that of elevated mutation rates over very short timescales, such as those presented in studies of pedigrees (e.g., Howell et al. 2003, Millar et al. 2008) and mutation accumulation lines (e.g., Denver et al. 2000, Haag-Liautard et al. 2008). In contrast, much lower rates are observed over evolutionary timescales, as estimated in phylogenetic analyses calibrated with reference to paleontological or geological data.

The disparity between rates of spontaneous mutation and evolutionary substitution can exceed an order of magnitude. Intermediate rates are expected between these two ends of the spectrum, but there has been disagreement over the exact form of the decline from the mutation rate to the substitution rate. Some authors have suggested that elevated mutation rates are very short-lived, perhaps persisting for only a small number of generations ( Macaulay et al. 1997, Gibbons 1998). More recently, it was proposed that the estimated rate decays exponentially over tens to hundreds of thousands of years, producing a “time dependence” of rates, whereby the magnitude of the inferred rate depends on the age of the calibration used in the analysis (Ho et al. 2005, Ho et al. 2007c, Penny 2005, Ho and Larson 2006). Although some of the original evidence for this hypothesis has been challenged ( Emerson 2007, Bandelt 2008), there has been a steady accumulation of empirical and theoretical support for a prolonged elevation of short-term rates (e.g., Genner et al. 2007, Burridge et al. 2008, Henn et al. 2009, Peterson and Masel 2009, …