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表征指猴的种系突变率和模式。

Characterizing the rates and patterns of germline mutations in the aye-aye ().

作者信息

Versoza Cyril J, Ehmke Erin E, Jensen Jeffrey D, Pfeifer Susanne P

机构信息

Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, USA.

Duke Lemur Center, Durham, NC, USA.

出版信息

bioRxiv. 2024 Nov 11:2024.11.08.622690. doi: 10.1101/2024.11.08.622690.

Abstract

Given the many levels of biological variation in mutation rates observed to date in primates - spanning from species to individuals to genomic regions - future steps in our understanding of mutation rate evolution will be aided by both a greater breadth of species coverage across the primate clade, but also by a greater depth as afforded by an evaluation of multiple trios within individual species. In order to help bridge these gaps, we here present an analysis of a species representing one of the most basal splits on the primate tree (aye-ayes), combining whole-genome sequencing of seven parent-offspring trios from a three-generation pedigree with a novel computational pipeline that takes advantage of recently developed pan-genome graphs, thereby circumventing the application of (highly subjective) quality metrics that has previously been shown to result in notable differences in the detection of mutations, and ultimately estimates of mutation rates. This deep sampling has enabled both a detailed picture of parental age effects as well as sex dependency in mutation rates which we here compare with previously studied primates, but has also provided unique insights into the nature of genetic variation in one of the most endangered primates on the planet.

摘要

鉴于迄今为止在灵长类动物中观察到的突变率存在许多层次的生物学变异——从物种到个体再到基因组区域——未来在我们对突变率进化的理解上取得进展,将得益于灵长类进化枝中更广泛的物种覆盖范围,也得益于对单个物种内多个三联体进行评估所带来的更深入研究。为了帮助弥合这些差距,我们在此展示对一种代表灵长类树最基部分支之一的物种(指狐猴)的分析,将来自一个三代家系的七个亲子三联体的全基因组测序与一种新颖的计算流程相结合,该流程利用了最近开发的泛基因组图谱,从而避免了应用(高度主观的)质量指标,此前已表明这些指标会导致在突变检测以及最终突变率估计上出现显著差异。这种深度采样不仅使我们能够详细了解亲代年龄效应以及突变率的性别依赖性,并在此与之前研究过的灵长类动物进行比较,还为地球上最濒危的灵长类动物之一的遗传变异本质提供了独特见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea6/11601268/a23a50761f26/nihpp-2024.11.08.622690v1-f0001.jpg

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