Molecular and Computational Biology, University of Southern California, Los Angeles, California.
Department of Applied Mathematics, St. Petersburg State Polytechnic University, St. Petersburg, Russia.
Evol Dev. 2019 May;21(3):157-171. doi: 10.1111/ede.12283. Epub 2019 Feb 12.
Robustness in development allows for the accumulation of genetically based variation in expression. However, this variation is usually examined in response to large perturbations, and examination of this variation has been limited to being spatial, or quantitative, but because of technical restrictions not both. Here we bridge these gaps by investigating replicated quantitative spatial gene expression using rigorous statistical models, in different genotypes, sexes, and species (Drosophila melanogaster and D. simulans). Using this type of quantitative approach with molecular developmental data allows for comparison among conditions, such as different genetic backgrounds. We apply this approach to the morphogenetic furrow, a wave of differentiation that patterns the developing eye disc. Within the morphogenetic furrow, we focus on four genes, hairy, atonal, hedgehog, and Delta. Hybridization chain reaction quantitatively measures spatial gene expression, co-staining for all four genes simultaneously. We find considerable variation in the spatial expression pattern of these genes in the eye between species, genotypes, and sexes. We also find that there has been evolution of the regulatory relationship between these genes, and that their spatial interrelationships have evolved between species. This variation has no phenotypic effect, and could be buffered by network thresholds or compensation from other genes. Both of these mechanisms could potentially be contributing to long term developmental systems drift.
发育稳健性允许基于遗传的表达变异的积累。然而，这种变异通常是在对大的扰动做出反应时进行检查的，而且这种变异的检查仅限于空间的或定量的，而不是两者兼而有之，因为技术限制。在这里，我们通过使用严格的统计模型，在不同的基因型、性别和物种（黑腹果蝇和 D. simulans）中研究重复的定量空间基因表达，来弥合这些差距。使用这种类型的定量方法进行分子发育数据的分析，可以在不同的条件（如不同的遗传背景）之间进行比较。我们将这种方法应用于形态发生沟，这是一种分化波，它塑造了正在发育的眼球。在形态发生沟内，我们集中研究四个基因， hairy、atonal、hedgehog 和 Delta。杂交链反应定量测量空间基因表达，同时对所有四个基因进行共染色。我们发现，这些基因在物种、基因型和性别之间的空间表达模式存在相当大的差异。我们还发现，这些基因之间的调控关系已经进化，它们的空间相互关系也在物种之间进化。这种变异没有表型效应，可能被网络阈值或其他基因的补偿缓冲。这两种机制都可能是导致长期发育系统漂移的原因。
