Piasecka Barbara, Lichocki Paweł, Moretti Sébastien, Bergmann Sven, Robinson-Rechavi Marc
Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland.
PLoS Genet. 2013 Apr;9(4):e1003476. doi: 10.1371/journal.pgen.1003476. Epub 2013 Apr 25.
Developmental constraints have been postulated to limit the space of feasible phenotypes and thus shape animal evolution. These constraints have been suggested to be the strongest during either early or mid-embryogenesis, which corresponds to the early conservation model or the hourglass model, respectively. Conflicting results have been reported, but in recent studies of animal transcriptomes the hourglass model has been favored. Studies usually report descriptive statistics calculated for all genes over all developmental time points. This introduces dependencies between the sets of compared genes and may lead to biased results. Here we overcome this problem using an alternative modular analysis. We used the Iterative Signature Algorithm to identify distinct modules of genes co-expressed specifically in consecutive stages of zebrafish development. We then performed a detailed comparison of several gene properties between modules, allowing for a less biased and more powerful analysis. Notably, our analysis corroborated the hourglass pattern at the regulatory level, with sequences of regulatory regions being most conserved for genes expressed in mid-development but not at the level of gene sequence, age, or expression, in contrast to some previous studies. The early conservation model was supported with gene duplication and birth that were the most rare for genes expressed in early development. Finally, for all gene properties, we observed the least conservation for genes expressed in late development or adult, consistent with both models. Overall, with the modular approach, we showed that different levels of molecular evolution follow different patterns of developmental constraints. Thus both models are valid, but with respect to different genomic features.
发育限制被认为会限制可行表型的空间，从而塑造动物进化。这些限制被认为在胚胎发育早期或中期最为强烈，分别对应早期保守模型或沙漏模型。已有相互矛盾的结果报道，但在最近对动物转录组的研究中，沙漏模型更受青睐。研究通常报告在所有发育时间点对所有基因计算的描述性统计数据。这会在比较的基因集之间引入依赖性，并可能导致有偏差的结果。在这里，我们使用另一种模块化分析方法克服了这个问题。我们使用迭代特征算法来识别在斑马鱼发育的连续阶段特异性共表达的不同基因模块。然后，我们对模块之间的几个基因特性进行了详细比较，从而进行偏差较小且更强大的分析。值得注意的是，与之前的一些研究不同，我们的分析在调控水平上证实了沙漏模式，调控区域序列在发育中期表达的基因中最为保守，但在基因序列、年龄或表达水平上并非如此。早期保守模型在基因复制和产生方面得到支持，即在早期发育中表达的基因最为罕见。最后，对于所有基因特性，我们观察到在发育后期或成体中表达的基因保守性最低，这与两个模型均相符。总体而言，通过模块化方法，我们表明不同水平的分子进化遵循不同的发育限制模式。因此，两个模型都是有效的，但针对的是不同的基因组特征。
