據(jù)《自然》雜志在線報道,，來自美國,、澳大利亞、英國和加拿大的國際科學家聯(lián)合小組已于近日完成了對灰色短尾負鼠（Monodelphis domestica）的基因組測序工作,。負鼠成為了首種被完整測序的有袋動物,，加入了此前完成測序的白鼠,、老鼠、黑猩猩以及人類等哺乳動物大家庭,。相關(guān)論文以封面文章的形式發(fā)表在5月10日的《自然》雜志上。
灰色短尾負鼠是南美60種樹棲有袋動物之一,，生活在玻利維亞、巴西和巴拉圭的熱帶雨林之中,，比它的澳大利亞表兄——考拉和袋鼠更具有嚙齒動物的代表特性。盡管短尾負鼠沒有標志性的育兒袋,，但卻有極短的懷孕期（約14天），它的幼崽通過附著在母親身上完成發(fā)育,。
澳大利亞科學研究委員會Australian Research Council（ARC）袋鼠基因組研究中心副主任Marilyn Renfree表示，負鼠基因組測序工作的完成十分重要,，因為它為哺乳動物進化的比較研究提供了新的參考點。人類所屬的胚胎動物與有袋動物在大約1.8億年前開始分化,，并沿著各自的道路不斷進化。參與該研究的麻省理工和哈佛大學Broad研究院院長Eric Lander也表示,，“負鼠是人類基因組的極佳參照,。”
研究結(jié)果顯示，負鼠的蛋白編碼基因（用于產(chǎn)生蛋白質(zhì)的基因）數(shù)量介于1萬8千個和2萬個之間,，與人類大體相當。同時,，大多數(shù)負鼠基因與胚胎動物的相同,，還有少數(shù)一些是有袋動物所特有的,。這些特有的基因與負鼠的感官知覺,、解毒作用和免疫系統(tǒng)密切相關(guān),，對它們適應特殊的生存環(huán)境至關(guān)重要。
此外,，研究人員還注意到，與胚胎動物十分類似,，負鼠新近的基因突變和進化大都沒有發(fā)生在蛋白編碼基因片段上，而是在所謂的“垃圾DNA”區(qū)域,?？茖W家認為，這些非基因片斷對基因表達形成蛋白質(zhì)的方式有重要的影響,。Lander則表示,，哺乳動物的奧秘就在于更多地創(chuàng)造新的基因表達調(diào)控方式，而不是新的蛋白編碼基因,。
灰色短尾負鼠從眾多有袋動物中“脫穎而出”,，很重要的一個原因是它作為人類疾病、發(fā)展生物學和免疫遺傳學的模型,，被廣泛地用于實驗研究。新出生的負鼠幼崽能夠從嚴重的脊索疾病中恢復過來,，因此被用于神經(jīng)系統(tǒng)再生研究。
研究小組成員之一,、澳大利亞科學研究委員會袋鼠基因組研究中心主任Jennifer Graves表示，對負鼠神經(jīng)疾病康復的潛在分子機制的認識和理解,，有望為人類相關(guān)疾病的治療開辟新的道路。Graves特別指出,，灰色短尾負鼠是除人類外唯一會出現(xiàn)惡性黑色素瘤（melanoma）的動物。
負鼠基因組測定的完成同時糾正了人類的一個錯誤的認識,，即有袋動物十分古老,，應屬于二等哺乳動物,。Graves表示,，負鼠具有一個編碼特殊T細胞受體的基因,，而在胚胎哺乳動物中并沒有發(fā)現(xiàn),，這給了之前的認識“當頭一棒”,。她說，“盡管負鼠的免疫系統(tǒng)十分古老,，但卻有著‘天壤之別’。”（任霄鵬/編譯）
生物谷 援引
原始出處：
Nature 447, 167-177 (10 May 2007) | doi:10.1038/nature05805; Received 5 December 2006; Accepted 3 April 2007
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
Tarjei S. Mikkelsen1,2, Matthew J. Wakefield3, Bronwen Aken4, Chris T. Amemiya5, Jean L. Chang1, Shannon Duke6, Manuel Garber1, Andrew J. Gentles7,8, Leo Goodstadt9, Andreas Heger9, Jerzy Jurka8, Michael Kamal1, Evan Mauceli1, Stephen M. J. Searle4, Ted Sharpe1, Michelle L. Baker10, Mark A. Batzer11, Panayiotis V. Benos12, Katherine Belov13, Michele Clamp1, April Cook1, James Cuff1, Radhika Das14, Lance Davidow15, Janine E. Deakin16, Melissa J. Fazzari17, Jacob L. Glass17, Manfred Grabherr1, John M. Greally17, Wanjun Gu18, Timothy A. Hore16, Gavin A. Huttley19, Michael Kleber1, Randy L. Jirtle14, Edda Koina16, Jeannie T. Lee15, Shaun Mahony12, Marco A. Marra20, Robert D. Miller10, Robert D. Nicholls21, Mayumi Oda17, Anthony T. Papenfuss3, Zuly E. Parra10, David D. Pollock18, David A. Ray22, Jacqueline E. Schein20, Terence P. Speed3, Katherine Thompson16, John L. VandeBerg23, Claire M. Wade1,24, Jerilyn A. Walker11, Paul D. Waters16, Caleb Webber9, Jennifer R. Weidman14, Xiaohui Xie1, Michael C. Zody1Broad Institute Genome Sequencing Platform and Broad Institute Whole Genome Assembly Team and , Jennifer A. Marshall Graves16, Chris P. Ponting9, Matthew Breen6,25, Paul B. Samollow26, Eric S. Lander1,27 & Kerstin Lindblad-Toh1
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville Victoria 3050, Australia
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Molecular Genetics Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
Stanford University School of Medicine, P060 Lucas Center, Stanford, California 94305, USA
Genetic Information Research Institute, 1925 Landings Drive, Mountain View, California 94043, USA
MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
Department of Biology, Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, New Mexico 87131, USA
Department of Biological Sciences, Biological Computation and Visualization Center, Center for Bio-Modular Multi-Scale Systems, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA
Department of Computational Biology, University of Pittsburgh, 3501 Fifth Avenue, Suite 3064, BST3, Pittsburgh, Pennsylvania 15260, USA
Faculty of Veterinary Science, University of Sydney, New South Wales 2006, Australia
Department of Radiation Oncology, Duke University Medical Center, Box 3433, Durham, North Carolina 27710, USA
Department of Molecular Biology, Hughes Medical Institute, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, The Australian National University, Canberra, ACT 2601, Australia
Department of Medicine (Hematology) and Molecular Genetics, Albert Einstein College of Medicine, Ullmann 911, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, MS 8101, 12801 17th Avenue, Aurora, Colorado 80045, USA
John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
Genome Sciences Centre, British Columbia Cancer Agency, 570 West 7th Avenue, Vancouver, British Columbia V5Z 4S6, Canada
Department of Pediatrics, Research Center Children's Hospital of Pittsburgh, 3460 Fifth Avenue, Room 2109, Rangos, Pittsburgh, Pennsylvania 15213, USA
Department of Biology, West Virginia University, Morgantown, West Virginia 26505, USA
Department of Genetics and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA
Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Center for Comparative Medicine and Translational Research, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
Department of Veterinary Integrative Biosciences, Texas A&M University, 4458 TAMU, College Station, Texas 77843, USA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Correspondence to: Tarjei S. Mikkelsen1,2Eric S. Lander1,27Kerstin Lindblad-Toh1 Correspondence and requests for materials should be addressed to K.L.-T. (Email: [email protected]), T.S.M. (Email: [email protected]) and E.S.L. (Email: [email protected]).
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Abstract
We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
