Emerson Brent C, Alvarado-Serrano Diego F, Hickerson Michael J
Island Ecology and Evolution Research Group, Instituto de Productos Naturales y Agrobiología (IPNA-CSIC), C/Astrofísico Francisco Sánchez 3, La Laguna, 38206, Spain.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Mol Ecol. 2015 Dec;24(24):6013-20. doi: 10.1111/mec.13451.
While welcoming the comment of Ho et al. (2015), we find little that undermines the strength of our criticism, and it would appear they have misunderstood our central argument. Here we respond with the purpose of reiterating that we are (i) generally critical of much of the evidence presented in support of the time-dependent molecular rate (TDMR) hypothesis and (ii) specifically critical of estimates of μ derived from tip-dated sequences that exaggerate the importance of purifying selection as an explanation for TDMR over extended timescales. In response to assertions put forward by Ho et al. (2015), we use panmictic coalescent simulations of temporal data to explore a fundamental assumption for tip-dated tree shape and associated mutation rate estimates, and the appropriateness and utility of the date randomization test. The results reveal problems for the joint estimation of tree topology, effective population size and μ with tip-dated sequences using BEAST. Given the simulations, BEAST consistently obtains incorrect topological tree structures that are consistent with the substantial overestimation of μ and underestimation of effective population size. Data generated from lower effective population sizes were less likely to fail the date randomization test yet still resulted in substantially upwardly biased estimates of rates, bringing previous estimates of μ from temporally sampled DNA sequences into question. We find that our general criticisms of both the hypothesis of time-dependent molecular evolution and Bayesian methods to estimate μ from temporally sampled DNA sequences are further reinforced.
在欢迎何等人（2015年）的评论的同时，我们发现几乎没有什么能削弱我们批评的力度，而且他们似乎误解了我们的核心论点。在此我们做出回应，目的是重申我们（i）总体上对支持时间依赖性分子速率（TDMR）假说的许多证据持批评态度，以及（ii）特别批评从末端定年序列得出的μ的估计值，这些估计值夸大了净化选择在长时间尺度上作为TDMR解释的重要性。针对何等人（2015年）提出的断言，我们使用时间数据的随机交配合并模拟来探讨末端定年树形和相关突变率估计的一个基本假设，以及日期随机化检验的适当性和实用性。结果揭示了使用BEAST对末端定年序列进行树形拓扑、有效种群大小和μ的联合估计存在的问题。鉴于模拟结果，BEAST始终获得与μ的大幅高估和有效种群大小的低估相一致的错误拓扑树形结构。从较低有效种群大小生成的数据不太可能通过日期随机化检验，但仍然导致速率估计值大幅向上偏差，这使得先前从时间采样的DNA序列得出的μ的估计值受到质疑。我们发现，我们对时间依赖性分子进化假说以及从时间采样的DNA序列估计μ的贝叶斯方法的总体批评得到了进一步加强。
