Soni Vivak, Versoza Cyril J, Jensen Jeffrey D, Pfeifer Susanne P
bioRxiv. 2025 Jul 4:2025.07.01.662565. doi: 10.1101/2025.07.01.662565.
The common marmoset is an important model in biomedical and clinical research, particularly for the study of age-related, neurodegenerative, and neurodevelopmental disorders (due to their biological similarities with humans), infectious disease (due to their susceptibility to a variety of pathogens), as well as developmental biology (due to their short gestation period relative to many other primates). Yet, despite being one of the most commonly used non-human primate models for research, the population genomics of the common marmoset remains relatively poorly characterized, despite the critical importance of this knowledge in many areas of research including genome-wide association studies, models of polygenic risk scores, and scans for the targets of selection. This neglect owes, at least in part, to two biological peculiarities related to the reproductive mode of the species - frequent twinning and sibling chimerism - which are likely to affect standard population genetic approaches relying on assumptions underlying the Wright-Fisher model. Using high-quality population genomic data, we here infer the rates and landscapes of mutation and recombination - two fundamental processes dictating the levels and patterns of genetic variability - in the presence of these biological features and discuss our findings in light of recent work in primates. Our results suggest that, while the species exhibits relatively low neutral mutation rates, rates of recombination are in the range of those observed in other anthropoids. Moreover, the recombination landscape of common marmosets, like that of many vertebrates, is dominated by PRDM9-mediated hotspots, with artificial intelligence-based models predicting an intricate 3D-structure of the species-specific PRDM9-DNA binding complex . Apart from providing novel insights into the population genetics of common marmosets, given the importance of the availability of fine-scale maps of mutation and recombination for evolutionary inference, this work will also serve as a valuable resource to aid future genomic research in this widely studied system.
普通狨猴是生物医学和临床研究中的重要模型,特别是在研究与年龄相关的、神经退行性和神经发育障碍方面(因其与人类的生物学相似性),传染病研究方面(因其对多种病原体易感),以及发育生物学方面(因其妊娠期相对于许多其他灵长类动物较短)。然而,尽管普通狨猴是研究中最常用的非人类灵长类动物模型之一,但其群体基因组学特征仍然相对较少,尽管这些知识在包括全基因组关联研究、多基因风险评分模型以及选择目标扫描等许多研究领域至关重要。这种忽视至少部分归因于与该物种繁殖模式相关的两个生物学特性——频繁孪生和同胞嵌合体,这可能会影响依赖赖特 - 费希尔模型假设的标准群体遗传学方法。利用高质量的群体基因组数据,我们在此推断在这些生物学特征存在的情况下突变和重组的速率及图谱——这两个决定遗传变异水平和模式的基本过程,并根据灵长类动物的近期研究讨论我们的发现。我们的结果表明,虽然该物种表现出相对较低的中性突变率,但重组率在其他类人猿观察到的范围内。此外,普通狨猴的重组图谱,与许多脊椎动物一样,由PRDM9介导的热点主导,基于人工智能的模型预测了物种特异性PRDM9 - DNA结合复合物的复杂三维结构。除了为普通狨猴的群体遗传学提供新的见解外,鉴于精细尺度的突变和重组图谱对于进化推断的重要性,这项工作还将作为宝贵资源,有助于该广泛研究系统未来的基因组研究。