Spanier Katina I, Jansen Mieke, Decaestecker Ellen, Hulselmans Gert, Becker Dörthe, Colbourne John K, Orsini Luisa, De Meester Luc, Aerts Stein
Department of Biology, Laboratory of Aquatic Ecology, Evolution and Conservation, KU Leuven, Belgium.
Department of Human Genetics, Laboratory of Computational Biology, KU Leuven, Belgium.
Genome Biol Evol. 2017 Jun 1;9(6):1821-1842. doi: 10.1093/gbe/evx127.
Ecological genomics aims to understand the functional association between environmental gradients and the genes underlying adaptive traits. Many genes that are identified by genome-wide screening in ecologically relevant species lack functional annotations. Although gene functions can be inferred from sequence homology, such approaches have limited power. Here, we introduce ecological regulatory genomics by presenting an ontology-free gene prioritization method. Specifically, our method combines transcriptome profiling with high-throughput cis-regulatory sequence analysis in the water fleas Daphnia pulex and Daphnia magna. It screens coexpressed genes for overrepresented DNA motifs that serve as transcription factor binding sites, thereby providing insight into conserved transcription factors and gene regulatory networks shaping the expression profile. We first validated our method, called Daphnia-cisTarget, on a D. pulex heat shock data set, which revealed a network driven by the heat shock factor. Next, we performed RNA-Seq in D. magna exposed to the cyanobacterium Microcystis aeruginosa. Daphnia-cisTarget identified coregulated gene networks that associate with the moulting cycle and potentially regulate life history changes in growth rate and age at maturity. These networks are predicted to be regulated by evolutionary conserved transcription factors such as the homologues of Drosophila Shavenbaby and Grainyhead, nuclear receptors, and a GATA family member. In conclusion, our approach allows prioritising candidate genes in Daphnia without bias towards prior knowledge about functional gene annotation and represents an important step towards exploring the molecular mechanisms of ecological responses in organisms with poorly annotated genomes.
生态基因组学旨在了解环境梯度与适应性性状潜在基因之间的功能关联。许多通过对具有生态相关性的物种进行全基因组筛选鉴定出的基因缺乏功能注释。尽管基因功能可从序列同源性推断，但此类方法的效力有限。在此，我们通过提出一种无本体基因优先级排序方法引入生态调控基因组学。具体而言，我们的方法将转录组分析与水蚤（大型溞和蚤状溞）中的高通量顺式调控序列分析相结合。它筛选共表达基因以寻找作为转录因子结合位点的过度富集的DNA基序，从而深入了解塑造表达谱的保守转录因子和基因调控网络。我们首先在蚤状溞热休克数据集上验证了我们称为Daphnia - cisTarget的方法，该数据集揭示了一个由热休克因子驱动的网络。接下来，我们对暴露于铜绿微囊藻的大型溞进行了RNA测序。Daphnia - cisTarget鉴定出与蜕皮周期相关且可能调节生长速率和成熟年龄等生活史变化的共调控基因网络。预计这些网络受进化保守转录因子调控，如果蝇光裸宝贝和粒头蛋白的同源物、核受体以及一个GATA家族成员。总之，我们的方法能够在不偏向功能基因注释先验知识的情况下对水蚤中的候选基因进行优先级排序，代表了朝着探索基因组注释不佳的生物体生态反应分子机制迈出的重要一步。
