Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
Proteins. 2010 Jul;78(9):2075-89. doi: 10.1002/prot.22723.
Model organisms such as yeast, fly, and worm have played a defining role in the study of many biological systems. A significant challenge remains in translating this information to humans. Of critical importance is the ability to differentiate those components where knowledge of function and interactions may be reliably inferred from those that represent lineage-specific innovations. To address this challenge, we use chromatin modification (CM) as a model system for exploring the evolutionary properties of their components in the context of their known functions and interactions. Collating previously identified components of CM from yeast, worm, fly, and human, we identified a "core" set of 50 CM genes displaying consistent orthologous relationships that likely retain their interactions and functions across taxa. In addition, we catalog many components that demonstrate lineage specific expansions and losses, highlighting much duplication within vertebrates that may reflect an expanded repertoire of regulatory mechanisms. Placed in the context of a high-quality protein-protein interaction network, we find, contrary to existing views of evolutionary modularity, that CM complex components display a mosaic of evolutionary histories: a core set of highly conserved genes, together with sets displaying lineage specific innovations. Although focused on CM, this study provides a template for differentiating those genes which are likely to retain their functions and interactions across species. As such, in addition to informing on the evolution of CM as a system, this study provides a set of comparative genomic approaches that can be generally applied to any biological systems.
模式生物，如酵母、果蝇和线虫，在许多生物系统的研究中发挥了重要作用。然而，将这些信息转化到人类身上仍然是一个重大的挑战。至关重要的是，能够区分那些功能和相互作用的知识可以从那些代表谱系特异性创新的知识中可靠推断出来的成分。为了应对这一挑战，我们使用染色质修饰 (CM) 作为模型系统，在其已知功能和相互作用的背景下探索其成分的进化特性。我们从酵母、线虫、果蝇和人类中整理了先前鉴定的 CM 成分，确定了一组“核心”的 50 个 CM 基因，它们具有一致的同源关系，可能在分类群中保留其相互作用和功能。此外，我们还对许多表现出线系特异性扩张和缺失的成分进行了编目，突出了脊椎动物内部的大量重复，这可能反映了调节机制的扩展 repertoire。将其置于高质量蛋白质-蛋白质相互作用网络的背景下，我们发现，与现有的进化模块性观点相反，CM 复合物成分显示出进化历史的镶嵌性：一组高度保守的核心基因，以及一组显示出线系特异性创新的基因。虽然这项研究集中在 CM 上，但它为区分那些在物种间可能保留其功能和相互作用的基因提供了一个模板。因此，除了为 CM 作为一个系统的进化提供信息外，这项研究还提供了一套比较基因组方法，可以广泛应用于任何生物系统。
