The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others. By applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift. I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect.

中文翻译：

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平衡对人类线粒体 DNA 分子钟的时间依赖性影响。


分子钟是估计进化时间尺度的重要遗传工具。然而，检测替代率估计的时间依赖性影响使其应用变得复杂。有人认为，人口变化过程可能是造成这种混杂效应的主要原因。在本研究中，我提出了一种新算法，用于估计系统发育相关序列的合并年龄，同时考虑到观察到的对其他人检测到的分子速率的时间依赖性影响。通过将此方法应用于具有浅层和深层拓扑的真实人类线粒体 DNA 树，我获得了人类进化主要事件的分子年龄，其分子年龄比之前估计的要大得多。这些年龄与最新的考古学和古生物学记录非常一致，这些记录支持早期解剖学现代人类在 315 ± 34 000 年前 (kya) 出现在非洲，以及早在 174 ± 48 000 年前就在非洲以外出现了现代现代人类。几年前。此外，在实施过程中，我证明了在规模波动的群体中，新的中性突变体的固定概率取决于有效群体规模，这更符合分子进化中性理论下的事实：分子突变的命运主要由随机漂移决定。我认为人口的人口统计历史比纯化选择和/或突变饱和对观察到的替代率的时间依赖性效应具有更决定性的影响，并且我提出了一种纠正这种效应的新方法。