美国伯克利国家实验室的科学家发现，切除老鼠超惰性染色体片断不仅没有影响老鼠的生活能力，也没有带来其他任何明显改变。有关专家指出，超惰性染色体在基因研究中有着重要意义，该研究成果减少了研究超惰性染色体的许多中间环节。相关研究包括发表在美国近期的《公共科学图书馆－生物学》杂志上。
3年前科研人员在人、老鼠和家鼠的染色体中发现了超过480个绝对相同的染色体片段，每一个片段的长度大于200个碱基对，这些染色体中至少有一半不转录也不编码任何蛋白质，因为它们的核苷酸排序是超惰性的，在这些片段中，诱变发生的速度很低。因此，研究人员认为，这些染色体在遗传编码中起着重要作用，对这些染色体的任何改变或变异都将对老鼠身体健康造成损害。另外还发现，超惰性不编码的染色体片段常常分布在一些重要基因附近，对周边基因的工作具有调节作用。这意味着，超惰性染色体片段应该负责生命中一些很重要的功能，但具体功能至今还不明确。
为了搞清楚这一问题，美国科学家用4种转基因老鼠进行实验，将每一个老鼠中的一种超惰性染色体片段切除。
实验结果发现，这些实验老鼠并没有因切除掉一种超惰性染色体片段而影响其生命健康和发育：老鼠的寿命没有降低，繁衍后代的能力依然正常。6种标准生化检测同时发现，这些实验老鼠体内的物质交换过程也能正常进行，甚至连被切除片段附近的基因活性也没有发生变化。唯一的不足是：在102只被切除了UC329超惰性染色体片段的实验老鼠中，有2只出生后只有一个肾，而正常情况下这一比例应为0．1％。
研究人员认为，该科研成果减少了研究超惰性染色体的许多中间环节，超惰性染色体片段的功能既与机体的基础生理机能无关，也与正常情况下个体发育的调节无关。(援引科技日报)
原始出处:
PLoS Biology
Deletion of Ultraconserved Elements Yields Viable Mice
Nadav Ahituv1,2¤, Yiwen Zhu1, Axel Visel1, Amy Holt1, Veena Afzal1, Len A. Pennacchio1,2, Edward M. Rubin1,2*
1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 2 United States Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America
Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.
Received: May 15, 2007; Accepted: July 3, 2007; Published: September 4, 2007
Figure 1.Schematic of the Human Genomic Locations of the Four Ultraconserved Elements That Were Deleted
(A) uc248 region; (B) uc329 region; (C) uc467 region; (D) uc482 region. A black oval represents each ultraconserved element, while the embryos above the schematics represent observed positive enhancer activities captured through transgenic mouse testing at e11.5 for that element [6]. Stained embryos in boxes represent whole-mount in situ hybridizations of the specific gene at e11.5 (genes without stained embryos were negative for this assay at this time point). Exons and noncoding elements not shown to scale.
全文链接：http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050234
