Time Dependency of Molecular Rate Estimates and Systematic Overestimation of Recent Divergence Times

Abstract

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 high, short-term (< 1-2 Myr) mutation rate and the low, 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 protein-coding 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. We rule out the possibility that it is a spurious result arising from sequence errors, and find it 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 timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.

Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

“…It is known that many factors may influence viral substitution rates and their variation over time [72]. Various methodological biases probably influence the calculation of both short-and long-term rates and therefore could explain the large difference between these rates [3,5,73,74], which has also been observed in cellular organisms [75]. Specifically, it has been recently shown that pervasive purifying selection could be one of the major obstacles in accurately estimating the ancient age of recent pathogens [76], and the development of substitution models accounting for this phenomenon are beginning to yield more realistic results [76,77].…”

Comparing Evolutionary Patterns and Variability in the Mitochondrial Control Region and Cytochrome b in Three Species of Baleen Whales

“…Yet such discrepancies may indicate that rate heterogeneity and other features of the control region in humans rapidly generate homoplasy that complicates estimates of rates. Recent studies on time dependence of molecular rates indicate that substitution rates are generally underestimated in a phylogenetic comparison of old divergences, and that comparing more recently diverged taxa provides better estimates of instantaneous substitution rates (Ho et al 2005;Ho and Larson 2006;Burridge et al 2008). For whales, fossil dates for divergences are old because the fossil record of modern species is poor.…”

Post-glacial partitioning of mitochondrial genetic variation in the field vole

“…Using this approach, a decay in nucleotide substitution rates with time has been identified across the population-species transition [3,4]. However, both the magnitude and the timing of any decay are hotly contested [5 -7], with particular focus on errors that may arise from the use of ancient DNA sequences to infer molecular rates [8 -10].…”