Varón-González Ceferino, Pallares Luisa F, Debat Vincent, Navarro Nicolas
Institut de Systématique, Évolution, Biodiversité, ISYEB - UMR 7205 - CNRS, MNHN, UPMC, EPHE, UA, Muséum National d'Histoire Naturelle, Sorbonne Universités, Paris, France.
Biogéosciences, UMR 6282 CNRS, Université Bourgogne Franche-Comté, Dijon, France.
Front Genet. 2019 Feb 12;10:64. doi: 10.3389/fgene.2019.00064. eCollection 2019.
The genetic architecture of skull shape has been extensively studied in mice and the results suggest a highly polygenic and additive basis. In contrast few studies have explored the genetic basis of the skull variability. Canalization and developmental stability are the two components of phenotypic robustness. They have been proposed to be emergent properties of the genetic networks underlying the development of the trait itself, but this hypothesis has been rarely tested empirically. Here we use outbred mice to investigate the genetic architecture of canalization of the skull shape by implementing a genome-wide marginal epistatic test on 3D geometric morphometric data. The same data set had been used previously to explore the genetic architecture of the skull mean shape and its developmental stability. Here, we address two questions: (1) Are changes in mean shape and changes in shape variance associated with the same genomic regions? and (2) Do canalization and developmental stability rely on the same loci and genetic architecture and do they involve the same patterns of shape variation? We found that unlike skull mean shape, among-individual shape variance and fluctuating asymmetry (FA) show a total lack of additive effects. They are both associated with complex networks of epistatic interactions involving many genes (protein-coding and regulatory elements). Remarkably, none of the genomic loci affecting mean shape contribute these networks despite their enrichment for genes involved in craniofacial variation and diseases. We also found that the patterns of shape FA and individual variation are largely similar and rely on similar multilocus epistatic genetic networks, suggesting that the processes channeling variation within and among individuals are largely common. However, the loci involved in these two networks are completely different. This in turn underlines the difference in the origin of the variation at these two levels, and points at buffering processes that may be specific to each level.
颅骨形状的遗传结构已在小鼠中得到广泛研究，结果表明其具有高度多基因和加性基础。相比之下，很少有研究探讨颅骨变异性的遗传基础。发育稳态和发育稳定性是表型稳健性的两个组成部分。它们被认为是该性状发育背后遗传网络的涌现特性，但这一假设很少经过实证检验。在这里，我们使用远交系小鼠，通过对三维几何形态测量数据进行全基因组边际上位性检验，来研究颅骨形状发育稳态的遗传结构。同一数据集先前已用于探索颅骨平均形状的遗传结构及其发育稳定性。在这里，我们解决两个问题：（1）平均形状的变化和形状方差的变化是否与相同的基因组区域相关？（2）发育稳态和发育稳定性是否依赖于相同的基因座和遗传结构，它们是否涉及相同的形状变异模式？我们发现，与颅骨平均形状不同，个体间形状方差和波动不对称性（FA）完全缺乏加性效应。它们都与涉及许多基因（蛋白质编码和调控元件）的复杂上位性相互作用网络相关。值得注意的是，尽管影响平均形状的基因组位点富含参与颅面变异和疾病的基因，但它们都不参与这些网络。我们还发现，形状FA和个体变异的模式在很大程度上相似，并且依赖于相似的多位点上位性遗传网络，这表明在个体内部和个体之间引导变异的过程在很大程度上是相同的。然而，参与这两个网络的基因座完全不同。这反过来强调了这两个水平变异起源的差异，并指出了可能特定于每个水平的缓冲过程。
