Evidence for time dependency of molecular rate estimates
Evidence for time dependency of molecular rate estimates
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DOI：
10.1080/10635150701435401
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发表时间：
2007-01-01
影响因子：
6.5
通讯作者：
Drummond, Alexei J.
中科院分区：
文献类型：
--
作者：
Ho, Simon Y. W.;Shapiro, Beth;Drummond, Alexei J.
种群基因组成的长期变化是通过固定新的突变而发生的，这一过程被称为替代。在中性条件下，种群中发生突变的速率和固定突变的速率预计是相等的(Kimura，1968)。从新突变的出现到其最终固定或丢失的命运之间，将会有一段时间它以短暂的多态形式存在于人群中(Kimura和Ohta，1971)。如果大多数突变是有害的(和非致命的)，这些瞬时多态的固定概率会降低，突变率将超过替换率(Kimura，1983)。因此，在分子进化过程的不同时间尺度上可以观察到不同的表观速率(Penny，2005；Penny和Holmes，2001)。传统上认为，鸟类和哺乳动物线粒体蛋白编码基因的替换率约为0.01个替换/位点/百万年(Myr)(Brown等人，1979；Ho，2007；Irwin等人，1991；Shields和Wilson，1987)，非编码D-环的进化速度要快几倍(例如，Pesole等人，1992；Quinn，1992)。在过去的十年中，越来越多的证据表明，在一系列生物体中，瞬时突变率大大超过替换率(例如，Denver等人，2000；Howell等人，2003；Lambert等人，2002；毛等人，2006；Mumm等人，1997；Parsons等人，1997；Santos等人，2005)。对第一个发现的直接反应是，由高突变率产生的多态是短暂的，可能只追溯到几百年前(Gibbons，1998；Macaulay等人，1997)。也就是说，净化选择被认为可以非常迅速地消除这些多态。最近，我们提出，这些多态持续的时间要长得多，如果不考虑这些多态，可能会导致对短期替代率的偏见估计(Ho等人，2005年)。此外，我们假设这种偏差的影响随着校准年龄的增加而可预测地下降，结果是在估计分歧时间的同时可以适应这种影响。这一假设是基于对鸟类和灵长类动物蛋白质编码基因的线粒体序列以及灵长类动物的D-loop序列的分析。这些分析的结果表明，估计速率的偏差可能会持续长达100万年，因此估计的速率最终会收敛到系统发育研究中估计的值。然而，我们分析的数据集的范围太有限，无法准确估计这种转变发生的确切时间框架，除了表明这种转变发生的时间似乎比之前认为的要长得多。这种关系的显著结果是，短期内估计的速率与时间尺度有关，这对最近进化事件的研究具有巨大的影响(Ho和Larson，2006；Penny，2005)。分子速率估计的时间依赖性远不是一个新的假设，它在文献中已经存在了十多年。韦恩等人(1991)在一项对食肉动物和灵长类动物的研究中首次明确描述了这种关系，发现替换率估计值随着时间深度的增加而线性下降。Garcia-Moreno(2004)在鸟类中发现了类似的模式，但下降是指数而不是线性的；这反映在我们的研究中，我们分析了类似的数据集(Ho等人，2005年)。Macaulay等人(1997年)认识到了这种关系的含义：“考虑到系谱比率可能明显高于…
Long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. The rate at which mutations arise in a population and the rate at which they are fixed are expected to be equal under neutral conditions (Kimura, 1968). Between the appearance of a new mutation and its eventual fate of fixation or loss, there will be a period in which it exists as a transient polymorphism in the population (Kimura and Ohta, 1971). If the majority of mutations are deleterious (and nonlethal), the fixation probabilities of these transient polymorphisms are reduced and the mutation rate will exceed the substitution rate (Kimura, 1983). Consequently, different apparent rates may be observed on different time scales of the molecular evolutionary process (Penny, 2005; Penny and Holmes, 2001). The substitution rate of the mitochondrial protein-coding genes of birds and mammals has been traditionally recognized to be about 0.01 substitutions/site/million years (Myr)(Brown et al., 1979; Ho, 2007; Irwin et al., 1991; Shields and Wilson, 1987), with the noncoding D-loop evolving several times more quickly (eg, Pesole et al., 1992; Quinn, 1992). Over the past decade, there has been mounting evidence that instantaneous mutation rates substantially exceed substitution rates, in a range of organisms (eg, Denver et al., 2000; Howell et al., 2003; Lambert et al., 2002; Mao et al., 2006; Mumm et al., 1997; Parsons et al., 1997; Santos et al., 2005). The immediate reaction to the first of these findings was that the polymorphisms generated by the elevated mutation rate are short-lived, perhaps extending back only a few hundred years (Gibbons, 1998; Macaulay et al., 1997). That is, purifying selection was thought to remove these polymorphisms very rapidly. Recently, we suggested that these polymorphisms persist for much longer and, if not accounted for, can lead to biased estimates of short-term substitution rates (Ho et al., 2005). Furthermore, we posited that the influence of this bias declines predictably with increasing age of the calibration, with the result that it can be accommodated while estimating divergence times. This hypothesis was based on analyses of mitochondrial sequences from the protein-coding genes of birds and primates, as well as D-loop sequences from primates. The results of these analyses indicated that the bias in rate estimates may persist for a period of up to 1 million years, whereupon estimated rates eventually converge on the values estimated in phylogenetic studies. The range of data sets we analyzed, however, was far too limited to provide accurate estimates of the exact time frame over which this transition occurs, apart from indicating that it appears to occur over a much longer period than previously thought. The noticeable consequence of this relationship is that rates estimated over the short-term are time scale dependent, which has enormous implications for studies of recent evolutionary events (Ho and Larson, 2006; Penny, 2005). The time dependency of molecular rate estimates, far from being a new hypothesis, had been present in the literature for well over a decade. Wayne et al.(1991) first described the relationship explicitly in a study of carnivores and primates, finding that substitution rate estimates decreased linearly with increasing time depth. Garcia-Moreno (2004) discovered a similar pattern in birds, but the decline was exponential rather than linear; this was mirrored in our study, in which we analyzed similar data sets (Ho et al., 2005). Macaulay et al.(1997) recognized the implications of such a relationship:" Given that the pedigree rate may be measurably higher than the …