Departament de Genètica i Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Nature. 2010 Mar 25;464(7288):583-6. doi: 10.1038/nature08838. Epub 2010 Mar 10.
The relationship between the genotype and the phenotype, or the genotype-phenotype map, is generally approached with the tools of multivariate quantitative genetics and morphometrics. Whereas studies of development and mathematical models of development may offer new insights into the genotype-phenotype map, the challenge is to make them useful at the level of microevolution. Here we report a computational model of mammalian tooth development that combines parameters of genetic and cellular interactions to produce a three-dimensional tooth from a simple tooth primordia. We systematically tinkered with each of the model parameters to generate phenotypic variation and used geometric morphometric analyses to identify, or developmentally ordinate, parameters best explaining population-level variation of real teeth. To model the full range of developmentally possible morphologies, we used a population sample of ringed seals (Phoca hispida ladogensis). Seal dentitions show a high degree of variation, typically linked to the lack of exact occlusion. Our model suggests that despite the complexity of development and teeth, there may be a simple basis for dental variation. Changes in single parameters regulating signalling during cusp development may explain shape variation among individuals, whereas a parameter regulating epithelial growth may explain serial, tooth-to-tooth variation along the jaw. Our study provides a step towards integrating the genotype, development and the phenotype.
基因型与表型之间的关系,或称为基因型-表型图谱,通常采用多元定量遗传学和形态计量学的工具来研究。尽管发育研究和发育数学模型可能为基因型-表型图谱提供新的见解,但挑战在于如何在微观进化层面上使其具有实际用途。在这里,我们报告了一个哺乳动物牙齿发育的计算模型,该模型将遗传和细胞相互作用的参数结合起来,从简单的牙齿原基中生成三维牙齿。我们系统地调整了模型的每个参数,以产生表型变异,并使用几何形态计量学分析来识别或发育排列最能解释真实牙齿群体水平变异的参数。为了模拟发育过程中可能出现的所有形态,我们使用了环斑海豹(Phoca hispida ladogensis)的种群样本。海豹的牙齿具有高度的变异,通常与咬合不精确有关。我们的模型表明,尽管牙齿发育过程复杂,但牙齿的变异可能具有简单的基础。在牙尖发育过程中调节信号的单个参数的变化可能解释了个体之间的形状变异,而调节上皮细胞生长的参数可能解释了沿着颌骨的牙齿之间的序列变异。我们的研究为整合基因型、发育和表型提供了一个步骤。
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