动物模型对研究脂代谢调控和代谢性疾病是必不可少的。模式生物秀丽线虫(Caenorhabditis elegans)是第一个全基因组被测序的真核生物(1998年)。
在过去的10多年中,由于其生活周期短、低成本、易培养和操作等优点,秀丽线虫成为一个研究脂代谢调控、肥胖和肥胖相关代谢性疾病发病机理的良好模式动物。然而,至今为止,我们不清楚,秀丽线虫基因组中有多少编码脂代谢酶的基因和参与的代谢途径,以及它们在果蝇、小鼠、大鼠和人中的保守性等。
梁斌课题组张玉茹博士等人研究秀丽线虫基因组发现,秀丽线虫21000个左右的基因中,至少有471个基因是编码脂代谢酶的基因,参与16条不同脂类的代谢途径。由此,他们构建了第一个秀丽线虫脂代谢基因数据库,绘制了第一张秀丽线虫脂代谢途径网络图。
同时,通过比较基因组学方法,他们进一步从人、小鼠、大鼠和果蝇基因组中分别发掘到581、585、563和428个脂代谢基因,其中,237个脂代谢基因在5个物种中都具有,70%以上的秀丽线虫脂代谢基因在人中是保守的。在581个人的脂代谢基因中,97个和代谢性疾病有关,其中有94个在秀丽线虫基因组中存在,表明秀丽线虫和人的脂代谢基因高度保守。
随后,利用秀丽线虫全基因组RNAi文库的优势,他们分析了356个脂代谢基因的生物学功能,发现有21个基因显著影响脂肪含量和生长发育等。该研究第一次从基因组的角度分析了秀丽线虫脂代谢基因及其代谢途径,为该领域未来的研究提供了大量有益的资源,同时也进一步支持秀丽线虫是研究脂代谢和代谢性疾病的良好动物模型。
该文章于近期在线发表于BMC Genomics。
Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans
Yuru Zhang, Xiaoju Zou, Yihong Ding, Haizhen Wang, Xiaoyun Wu and Bin Liang.
Background:Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics.
Results:We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions:This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases.