Lee Hui-Jie, Rodrigue Nicolas, Thorne Jeffrey L
Department of Statistics, North Carolina State University
Department of Biology, Carleton University, Ottawa, ON, Canada.
Mol Biol Evol. 2015 Aug;32(8):1948-61. doi: 10.1093/molbev/msv099. Epub 2015 Apr 29.
Rates of molecular evolution can vary over time. Diverse statistical techniques for divergence time estimation have been developed to accommodate this variation. These typically require that all sequence (or codon) positions at a locus change independently of one another. They also generally assume that the rates of different types of nucleotide substitutions vary across a phylogeny in the same way. This permits divergence time estimation procedures to employ an instantaneous rate matrix with relative rates that do not differ among branches. However, previous studies have suggested that some substitution types (e.g., CpG to TpG changes in mammals) are more clock-like than others. As has been previously noted, this is biologically plausible given the mutational mechanism of CpG to TpG changes. Through stochastic mapping of sequence histories from context-independent substitution models, our approach allows for context-dependent nucleotide substitutions to change their relative rates over time. We apply our approach to the analysis of a 0.15 Mb intergenic region from eight primates. In accord with previous findings, we find comparatively little rate variation over time for CpG to TpG substitutions but we find more for other substitution types. We conclude by discussing the limitations and prospects of our approach.
分子进化速率会随时间变化。为适应这种变化,已开发出多种用于分歧时间估计的统计技术。这些技术通常要求一个位点上的所有序列(或密码子)位置彼此独立变化。它们一般还假定不同类型核苷酸替换的速率在系统发育中以相同方式变化。这使得分歧时间估计程序能够采用一个瞬时速率矩阵,其相对速率在各分支间无差异。然而,先前的研究表明,某些替换类型(如哺乳动物中从CpG到TpG的变化)比其他类型更具时钟样特征。如前所述,考虑到从CpG到TpG变化的突变机制,这在生物学上是合理的。通过对与上下文无关的替换模型的序列历史进行随机映射,我们的方法允许与上下文相关的核苷酸替换随时间改变其相对速率。我们将我们的方法应用于对来自八种灵长类动物的0.15 Mb基因间区域的分析。与先前的发现一致,我们发现从CpG到TpG替换随时间的速率变化相对较小,但其他替换类型的速率变化较大。我们通过讨论我们方法的局限性和前景来结束本文。