鼩鼱基因组学关联牙齿的确定性和非确定性生长。

BACKGROUND: Continuously growing teeth are an important innovation in mammalian evolution, yet genetic regulation of continuous growth by stem cells remains incompletely understood. Dental stem cells responsible for tooth crown growth are lost at the onset of tooth root formation. Genetic signaling that initiates this loss is difficult to study with the ever-growing incisor and rooted molars of mice, the most common mammalian dental model species, because signals for root formation overlap with signals that pattern tooth size and shape (i.e., cusp patterns). Bank and prairie voles (Cricetidae, Rodentia, Glires) have evolved rooted and unrooted molars while retaining similar size and shape, providing alternative models for studying roots. RESULTS: We assembled a de novo genome of Myodes glareolus, a vole with high-crowned, rooted molars, and performed genomic and transcriptomic analyses in a broad phylogenetic context of Glires (rodents and lagomorphs) to assess differential selection and evolution in tooth forming genes. Bulk transcriptomics comparisons of embryonic molar development between bank voles and mice demonstrated overall conservation of gene expression levels, with species-specific differences corresponding to the accelerated and more extensive patterning of the vole molar. We leverage convergent evolution of unrooted molars across the clade to examine changes that may underlie the evolution of unrooted molars. We identified 15 dental genes with changing synteny relationships and six dental genes undergoing positive selection across Glires, two of which were undergoing positive selection in species with unrooted molars, Dspp and Aqp1. Decreased expression of both genes in prairie voles with unrooted molars compared to bank voles supports the presence of positive selection and may underlie differences in root formation. CONCLUSIONS: Our results support ongoing evolution of dental genes across Glires and identify candidate genes for mechanistic studies of root formation. Comparative research using the bank vole as a model species can reveal the complex evolutionary background of convergent evolution for ever-growing molars.

背景：不断生长的牙齿是哺乳动物进化的一个重要创新，然而，干细胞对连续生长的基因调控仍不完全了解。负责牙冠生长的牙干细胞在牙根形成时丧失。启动这种丧失的遗传信号很难用老鼠的不断生长的切牙和生根的磨牙（最常见的哺乳动物牙齿模型物种）进行研究，因为根形成的信号与牙齿大小和形状的模式（即尖峰模式）的信号重叠。田鼠（仓鼠科，啮齿目，Glire）进化出了生根和无根的磨牙，同时保持了相似的大小和形状，为研究根提供了替代模型。

结果：我们组装了田鼠的 Myodes glareolus 的从头基因组，并在 Glire（啮齿目和兔形目）的广泛系统发育背景下进行了基因组和转录组分析，以评估牙齿形成基因的差异选择和进化。田鼠和老鼠胚胎磨牙发育的批量转录组比较表明，基因表达水平总体上是保守的，物种特异性差异对应于田鼠磨牙的加速和更广泛的模式。我们利用该进化枝中无生根磨牙的趋同进化来研究可能导致无生根磨牙进化的变化。我们确定了 15 个牙齿基因的基因座发生了变化，6 个牙齿基因在Glires 中经历了正选择，其中两个基因在无生根磨牙的物种中经历了正选择，即 Dspp 和 Aqp1。与田鼠相比，无生根磨牙的草原田鼠的这两个基因的表达都减少了，这支持了正选择的存在，并可能是根形成差异的基础。

结论：我们的研究结果支持Glires 中牙齿基因的持续进化，并确定了根形成机制研究的候选基因。使用田鼠作为模型物种的比较研究可以揭示不断生长的磨牙趋同进化的复杂进化背景。