Alarm Bells for the Molecular Clock? No Support for Ho et al.'s Model of Time-Dependent Molecular Rate Estimates

In a recent paper, Ho et al. (2005) appear to have provided startling evidence for a relationship between the rate of molecular evolution and sampling time that they then describe with the fitting of vertically translated exponential decay curves. If correct, their results carry major implications for molecular evolutionary biology (Penny, 2005), and their work follows from the observed disparity between mitochondrial DNA (mtDNA) rate estimates directly measured from pedigree studies and those inferred from intraspecific and interspecific phylogenetic studies. A number of recent studies of control region mtDNA from detailed human pedigrees have reported exceptionally high estimates of mutation rate, summarized in Howell et al. (2003). Pooling data from two comparable Leber hereditary optic neuropathy studies (Howell et al., 1996, 2003), Howell et al. (2003) obtained a pedigree divergence rate of 1.0 mutations/bp/Myr (mutations per base pair per million years) for the control region. Building on these data, Howell et al. (2003) also combined data from a number of unrelated pedigree studies (Bendall et al., 1996; Cavelier et al., 2000; Heyer et al., 2001; Howell et al., 1996, 2003; Mumm et al., 1997; Parsons and Holland, 1998; Parsons et al., 1997; Sigurdardottir et al., 2000; Soodyall et al., 1997) and obtained a broadly similar control-region pedigree divergence rate of 0.95 mutations/bp/Myr. Ho et al. (2005) point out that this value is vastly greater (approximately 50×) than the phylogenetically derived divergence rate of approximately 0.02 mutations/bp/Myr for protein-coding mitochondrial DNA. However, it should be acknowledged that, as deduced from comparative phylogenetic studies, the control region evolves much faster than the protein-coding regions within human mitochondrial DNA. Thus, in real terms, pedigree mutation rates for the human mitochondrial control region appear to be approximately 5- to 10-fold higher than phylogenetically derived divergence rates of 0.087 to 0.236 mutations/bp/Myr (Hasegawa et al., 1993; Stoneking et al., 1992; Tamura and Nei, 1993).