据《自然》杂志在线报道，来自美国、澳大利亚、英国和加拿大的国际科学家联合小组已于近日完成了对灰色短尾负鼠（Monodelphis domestica）的基因组测序工作。负鼠成为了首种被完整测序的有袋动物，加入了此前完成测序的白鼠、老鼠、黑猩猩以及人类等哺乳动物大家庭。相关论文以封面文章的形式发表在5月10日的《自然》杂志上。
灰色短尾负鼠是南美60种树栖有袋动物之一，生活在玻利维亚、巴西和巴拉圭的热带雨林之中，比它的澳大利亚表兄——考拉和袋鼠更具有啮齿动物的代表特性。尽管短尾负鼠没有标志性的育儿袋，但却有极短的怀孕期（约14天），它的幼崽通过附着在母亲身上完成发育。
澳大利亚科学研究委员会Australian Research Council（ARC）袋鼠基因组研究中心副主任Marilyn Renfree表示，负鼠基因组测序工作的完成十分重要，因为它为哺乳动物进化的比较研究提供了新的参考点。人类所属的胚胎动物与有袋动物在大约1.8亿年前开始分化，并沿着各自的道路不断进化。参与该研究的麻省理工和哈佛大学Broad研究院院长Eric Lander也表示，“负鼠是人类基因组的极佳参照。”
研究结果显示，负鼠的蛋白编码基因（用于产生蛋白质的基因）数量介于1万8千个和2万个之间，与人类大体相当。同时，大多数负鼠基因与胚胎动物的相同，还有少数一些是有袋动物所特有的。这些特有的基因与负鼠的感官知觉、解毒作用和免疫系统密切相关，对它们适应特殊的生存环境至关重要。
此外，研究人员还注意到，与胚胎动物十分类似，负鼠新近的基因突变和进化大都没有发生在蛋白编码基因片段上，而是在所谓的“垃圾DNA”区域。科学家认为，这些非基因片断对基因表达形成蛋白质的方式有重要的影响。Lander则表示，哺乳动物的奥秘就在于更多地创造新的基因表达调控方式，而不是新的蛋白编码基因。
灰色短尾负鼠从众多有袋动物中“脱颖而出”，很重要的一个原因是它作为人类疾病、发展生物学和免疫遗传学的模型，被广泛地用于实验研究。新出生的负鼠幼崽能够从严重的脊索疾病中恢复过来，因此被用于神经系统再生研究。
研究小组成员之一、澳大利亚科学研究委员会袋鼠基因组研究中心主任Jennifer Graves表示，对负鼠神经疾病康复的潜在分子机制的认识和理解，有望为人类相关疾病的治疗开辟新的道路。Graves特别指出，灰色短尾负鼠是除人类外唯一会出现恶性黑色素瘤（melanoma）的动物。
负鼠基因组测定的完成同时纠正了人类的一个错误的认识，即有袋动物十分古老，应属于二等哺乳动物。Graves表示，负鼠具有一个编码特殊T细胞受体的基因，而在胚胎哺乳动物中并没有发现，这给了之前的认识“当头一棒”。她说，“尽管负鼠的免疫系统十分古老，但却有着‘天壤之别’。”（任霄鹏/编译）
生物谷 援引
原始出处：
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: kersli@broad.mit.edu), T.S.M. (Email: tarjei@broad.mit.edu) and E.S.L. (Email: lander@broad.mit.edu).
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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.
