美国纽约大学比较功能基因组学中心的生物学家发现,名为mel-28的基因具有双重作用,它既在细胞分裂时起确保染色体正常分裂的作用,又参与了核被膜(nuclearenvelope)功能。利用系统汇集实验证据手段,生物学家能够找到不同基因间的关联。阐述基因关联的网络图显示,大多数基因处在高度关联的、被称为模块的组群中,这些模块含有众多的基因,它们参与了相同的作用。
纽约大学研究人员法比欧•皮亚诺和安尼塔•弗南德泽的发现出自对秀丽隐杆线虫(C.elegans)的研究。该线虫是人类首次完成基因组排序的动物,同时也是帮助人们研究胚胎如何发育的模式生物。皮亚诺和弗南德泽发现,mel-28基因同网络图的大多数基因不同,它与两个独特的模块相关联。
通过线虫在胚胎早期时将mel-28基因与带有荧光标记GFP的基因熔融,皮亚诺和弗南德泽观察到了细胞在活胚胎中分裂时熔融物MEL-28-GFP的动向:在细胞核外围和染色体之间穿梭。进一步的功能测试实验显示,mel-28对核被膜的完整性和染色体分裂的正确性均具有重要的作用。
英文原文:
NYU biologists identify gene that coordinates two cellular processes
A team of biologists at New York University's Center for Comparative Functional Genomics has uncovered a dual role for the gene mel-28. The gene plays a part in ensuring that chromosomes are divided properly during cell division and it is required for nuclear envelope function. The findings appear in the journal Current Biology.
The team is using functional genomic tools to study the nematode worm Caenorhabditis elegans (C. elegans), the first animal species whose genome was completely sequenced and a model organism to study how embryos develop. The study appearing in Current Biology was performed by NYU's Fabio Piano, an assistant professor, and Anita Fernandez, a post-doctoral researcher, at the Center for Comparative Functional Genomics.
Biologists can draw connections between genes based on systematically accumulated experimental evidence. Network diagrams that illustrate such connections show that most genes fall into highly interconnected groups called modules. These modules are often enriched for genes that share the same role. In order to determine the functions of genes whose role is unknown, researchers examine genes in the same module whose function has already been discovered. This approach has proven useful for learning about the roles of unknown genes.
Unlike most genes in the network, mel-28 had connections to two distinct modules. Piano and Fernandez tested the idea that mel-28 plays important roles in both chromosome segregation and nuclear envelope function. Part of this undertaking included examining the protein MEL-28, which the gene mel-28 encodes.
By fusing mel-28 to a gene-encoding GFP, a fluorescent marker, and expressing this fusion in early embryos, they visualized the movement of MEL-28 during cell division in living embryos. Consistent with the idea that MEL-28 had function in chromosome segregation and the nuclear envelope, the MEL-28-GFP fusion was observed to shuttle between the nuclear periphery and the chromosomes during cell division. Additional functional tests showed that mel-28 was essential to both the integrity of the nuclear envelope and to proper chromosome segregation. This study served as a validation of network modeling as a means to identify genes that coordinate multiple functions.