Genome Biol Evol. 2010 Jul 12;2:284-92. doi: 10.1093/gbe/evq018.
The study of gene expression evolution in vertebrates has hitherto focused on the analysis of transcriptomes in tissues of different species. However, because a tissue is made up of different cell types, and cell types differ with respect to their transcriptomes, the analysis of tissues offers a composite picture of transcriptome evolution. The isolation of individual cells from tissue sections opens up the opportunity to study gene expression evolution at the cell type level. We have stained neurons and endothelial cells in human brains by antibodies against cell type-specific marker proteins, isolated the cells using laser capture microdissection, and identified genes preferentially expressed in the two cell types. We analyze these two classes of genes with respect to their expression in 62 different human tissues, with respect to their expression in 44 human "postmortem" brains from different developmental stages and with respect to between-species brain expression differences. We find that genes preferentially expressed in neurons differ less across tissues and developmental stages than genes preferentially expressed in endothelial cells. We also observe less expression differences within primate species for neuronal transcriptomes. In stark contrast, we see more gene expression differences between humans, chimpanzees, and rhesus macaques relative to within-species differences in genes expressed preferentially in neurons than in genes expressed in endothelial cells. This suggests that neuronal and endothelial transcriptomes evolve at different rates within brain tissue.
迄今为止,脊椎动物基因表达进化的研究主要集中在分析不同物种组织中的转录组。然而,由于组织是由不同的细胞类型组成的,而细胞类型在转录组方面存在差异,因此组织的分析提供了转录组进化的综合图像。从组织切片中分离出单个细胞为研究细胞类型水平的基因表达进化提供了机会。我们使用针对细胞类型特异性标记蛋白的抗体对人脑的神经元和内皮细胞进行染色,使用激光捕获显微切割分离细胞,并鉴定出在这两种细胞类型中优先表达的基因。我们分析了这两类基因在 62 个人体组织中的表达情况,在 44 个人类不同发育阶段的“死后”大脑中的表达情况,以及在不同物种大脑表达差异方面的情况。我们发现,在神经元中优先表达的基因在组织和发育阶段之间的差异小于在血管内皮细胞中优先表达的基因。我们还观察到灵长类动物的神经元转录本的内部表达差异较小。与此形成鲜明对比的是,与在神经元中优先表达的基因相比,我们在人类、黑猩猩和恒河猴之间看到了更多的基因表达差异,而在血管内皮细胞中表达的基因则相对较少。这表明神经元和血管内皮细胞的转录本在脑组织内以不同的速度进化。