Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Genome Res. 2013 Jun;23(6):1039-50. doi: 10.1101/gr.146233.112. Epub 2013 May 2.
Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study the evolution of the transcriptional response to heat shock in eight species of Ascomycota fungi and to reconstruct modules of the ancestral environmental stress response (ESR). We found substantial conservation in the stress response across species and in the reconstructed components of the ancestral ESR modules. The greatest divergence was in the most induced stress, primarily through module expansion. The divergence of the heat stress response exceeds that observed in the response to glucose depletion in the same species. Arboretum and its associated analyses provide a comprehensive framework to systematically study regulatory evolution of condition-specific responses.
比较功能基因组学通过分析跨物种的功能数据（如基因表达谱）来研究生物过程的进化。一个主要的挑战是比较在复杂系统发育中收集的谱。在这里，我们提出了 Arboretum，这是一种新颖的可扩展计算算法，它将来自多个物种的表达数据与物种和基因系统发育相结合，以推断现存物种中共同表达基因的模块及其进化历史。我们还开发了新的、普遍适用的基因调控模块的保守性和分歧性度量标准，以评估基因含量和表达变化对模块进化的影响。我们使用 Arboretum 研究了 8 种子囊菌真菌对热休克的转录反应的进化，并重建了祖先环境应激反应 (ESR) 的模块。我们发现，在物种间以及在重建的祖先 ESR 模块的组成部分中，应激反应存在着大量的保守性。最大的分歧主要是通过模块扩展在最诱导的应激中产生的。热应激反应的分歧超过了在相同物种中观察到的葡萄糖耗竭反应的分歧。Arboretum 及其相关分析为系统研究特定条件反应的调控进化提供了一个全面的框架。
