Zhao Yuqi, Sheng Zizhang, Huang Jingfei
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Mol Biosyst. 2012 Feb;8(2):504-10. doi: 10.1039/c1mb05415e. Epub 2011 Dec 12.
Animal models have been extensively used in the study of cardiovascular disease (CVD) and have provided important insights into disease pathogenesis and drug development. However, the level of conservation of gene expression patterns of the orthologous genes between human and animal models was unclear. To address this issue, we compared the expression of orthologous genes in human and four models (rhesus, rat, mouse and dog), based on 42 normal heart samples with high quality gene expression data. The results show that the global expression profiles between animal model and human orthologous genes are highly preserved. The phylogenetic tree inferred from the gene expression profiles has similar topology to that of the species tree. However, differentially expressed genes (DEGs) between human and each model were identified and these four gene datasets are enriched with different molecular functions, including hormone-receptor binding and geranyl transferase activity. The 65 overlapped DEGs between four sets are involved in thyroid cancer, proteasome systems, aminoacyl-tRNA biosynthesis and GST (Glycine, Serine and Threonine) metabolism, of which functions are divergent between models and humans. In addition, 46.2% (30/65) of the communal genes have been experimentally proven to be associated with cardiovascular disease. Next, we constructed a co-expression network based on intra- and inter-species variation, to elucidate the altered network organization. It indicates that these DEGs evolved as modules rather than independently. The integrated heart transcriptome data should provide a valuable resource for the in-depth understanding of cardiology and the development of cardiovascular disease models.
动物模型已广泛应用于心血管疾病（CVD）研究，并为疾病发病机制和药物开发提供了重要见解。然而，人类与动物模型之间直系同源基因的基因表达模式保守程度尚不清楚。为解决这一问题，我们基于42个具有高质量基因表达数据的正常心脏样本，比较了人类与四种模型（恒河猴、大鼠、小鼠和狗）中直系同源基因的表达情况。结果表明，动物模型与人类直系同源基因之间的整体表达谱高度保守。从基因表达谱推断出的系统发育树与物种树具有相似的拓扑结构。然而，我们鉴定出了人类与每种模型之间的差异表达基因（DEG），这四个基因数据集富含不同的分子功能，包括激素受体结合和香叶基转移酶活性。四组之间65个重叠的差异表达基因涉及甲状腺癌、蛋白酶体系统、氨酰-tRNA生物合成和谷胱甘肽S-转移酶（甘氨酸、丝氨酸和苏氨酸）代谢，其功能在模型和人类之间存在差异。此外，46.2%（30/65）的共有基因已通过实验证明与心血管疾病相关。接下来，我们基于种内和种间变异构建了一个共表达网络，以阐明网络组织的变化。结果表明，这些差异表达基因是作为模块而非独立进化的。整合的心脏转录组数据应为深入理解心脏病学和开发心血管疾病模型提供有价值的资源。
