美國伯克利國家實(shí)驗(yàn)室的科學(xué)家發(fā)現(xiàn),，切除老鼠超惰性染色體片斷不僅沒有影響老鼠的生活能力,，也沒有帶來其他任何明顯改變,。有關(guān)專家指出，超惰性染色體在基因研究中有著重要意義,，該研究成果減少了研究超惰性染色體的許多中間環(huán)節(jié)。相關(guān)研究包括發(fā)表在美國近期的《公共科學(xué)圖書館－生物學(xué)》雜志上,。
3年前科研人員在人、老鼠和家鼠的染色體中發(fā)現(xiàn)了超過480個絕對相同的染色體片段,，每一個片段的長度大于200個堿基對,，這些染色體中至少有一半不轉(zhuǎn)錄也不編碼任何蛋白質(zhì),，因?yàn)樗鼈兊暮塑账崤判蚴浅栊缘?，在這些片段中,，誘變發(fā)生的速度很低。因此,，研究人員認(rèn)為，這些染色體在遺傳編碼中起著重要作用,，對這些染色體的任何改變或變異都將對老鼠身體健康造成損害。另外還發(fā)現(xiàn),，超惰性不編碼的染色體片段常常分布在一些重要基因附近,，對周邊基因的工作具有調(diào)節(jié)作用,。這意味著，超惰性染色體片段應(yīng)該負(fù)責(zé)生命中一些很重要的功能,，但具體功能至今還不明確。
為了搞清楚這一問題,，美國科學(xué)家用4種轉(zhuǎn)基因老鼠進(jìn)行實(shí)驗(yàn)，將每一個老鼠中的一種超惰性染色體片段切除,。
實(shí)驗(yàn)結(jié)果發(fā)現(xiàn),，這些實(shí)驗(yàn)老鼠并沒有因切除掉一種超惰性染色體片段而影響其生命健康和發(fā)育：老鼠的壽命沒有降低,，繁衍后代的能力依然正常。6種標(biāo)準(zhǔn)生化檢測同時發(fā)現(xiàn),，這些實(shí)驗(yàn)老鼠體內(nèi)的物質(zhì)交換過程也能正常進(jìn)行,，甚至連被切除片段附近的基因活性也沒有發(fā)生變化。唯一的不足是：在102只被切除了UC329超惰性染色體片段的實(shí)驗(yàn)老鼠中,，有2只出生后只有一個腎，而正常情況下這一比例應(yīng)為0．1％。
研究人員認(rèn)為,，該科研成果減少了研究超惰性染色體的許多中間環(huán)節(jié),，超惰性染色體片段的功能既與機(jī)體的基礎(chǔ)生理機(jī)能無關(guān),，也與正常情況下個體發(fā)育的調(diào)節(jié)無關(guān)。(援引科技日報(bào))
原始出處:
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.
全文鏈接：http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050234
