哺乳动物突变谱的演变与趋同
The evolution and convergence of mutation spectra across mammals.
作者信息
Talenti Andrea, Wilkinson Toby, Morrison Liam J, Prendergast James G D
机构信息
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, UK.
出版信息
Commun Biol. 2025 May 17;8(1):763. doi: 10.1038/s42003-025-08181-x.
Despite the key role genetic mutations play in shaping phenotypic differences between species, little is currently known about the evolution of germline mutation spectra across mammals. Domesticated species are likely particularly interesting case studies because of their high mutation rates and complex evolutionary histories, which can span multiple founding events and genetic bottlenecks. Here we have developed a new reusable workflow, nSPECTRa, that can undertake the key steps in characterising mutation spectra, from determining ancestral alleles to characterising multiple forms of variation. We apply nSPECTRa to seven species, including several that have undergone domestication, and highlight how nSPECTRa can provide important insights into mutation rate evolution. While mutation spectra most often show marked differences between species and even breeds, certain mutation types have risen to a high frequency in subpopulations of different species, indicative of convergent evolution in mutation rates. This includes the previously characterized TCC- > TTC change enriched among European humans, which is also enriched among East Asian cattle. We show Indicine cattle are particularly interesting examples of how different mutation spectra segregate within a population and subsequently spread across the globe. Together, this work has important implications for understanding the control and evolution of mammalian mutation rates.
尽管基因突变在塑造物种间表型差异方面起着关键作用,但目前对于整个哺乳动物种系突变谱的进化了解甚少。家养物种可能是特别有趣的案例研究对象,因为它们具有高突变率和复杂的进化历史,其进化历史可能跨越多个奠基事件和基因瓶颈。在此,我们开发了一种新的可重复使用的工作流程nSPECTRa,它可以完成表征突变谱的关键步骤,从确定祖先等位基因到表征多种变异形式。我们将nSPECTRa应用于七个物种,包括几个已经驯化的物种,并强调nSPECTRa如何能够为突变率进化提供重要见解。虽然突变谱通常在物种甚至品种之间表现出显著差异,但某些突变类型在不同物种的亚群中出现频率很高,这表明突变率存在趋同进化。这包括之前在欧洲人群中富集的TCC->TTC变化,在东亚牛中也有富集。我们表明,瘤牛是不同突变谱如何在一个种群中分离并随后传播到全球的特别有趣的例子。这项工作对于理解哺乳动物突变率的控制和进化具有重要意义。