Article

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

  1. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
  2. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  3. Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville Victoria 3050, Australia
  4. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  5. Molecular Genetics Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA
  6. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
  7. Stanford University School of Medicine, P060 Lucas Center, Stanford, California 94305, USA
  8. Genetic Information Research Institute, 1925 Landings Drive, Mountain View, California 94043, USA
  9. MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
  10. Department of Biology, Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, New Mexico 87131, USA
  11. 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
  12. Department of Computational Biology, University of Pittsburgh, 3501 Fifth Avenue, Suite 3064, BST3, Pittsburgh, Pennsylvania 15260, USA
  13. Faculty of Veterinary Science, University of Sydney, New South Wales 2006, Australia
  14. Department of Radiation Oncology, Duke University Medical Center, Box 3433, Durham, North Carolina 27710, USA
  15. Department of Molecular Biology, Hughes Medical Institute, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
  16. ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, The Australian National University, Canberra, ACT 2601, Australia
  17. Department of Medicine (Hematology) and Molecular Genetics, Albert Einstein College of Medicine, Ullmann 911, 1300 Morris Park Avenue, Bronx, New York 10461, USA
  18. Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, MS 8101, 12801 17th Avenue, Aurora, Colorado 80045, USA
  19. John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia
  20. Genome Sciences Centre, British Columbia Cancer Agency, 570 West 7th Avenue, Vancouver, British Columbia V5Z 4S6, Canada
  21. Department of Pediatrics, Research Center Children's Hospital of Pittsburgh, 3460 Fifth Avenue, Room 2109, Rangos, Pittsburgh, Pennsylvania 15213, USA
  22. Department of Biology, West Virginia University, Morgantown, West Virginia 26505, USA
  23. Department of Genetics and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA
  24. Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
  25. Center for Comparative Medicine and Translational Research, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
  26. Department of Veterinary Integrative Biosciences, Texas A&M University, 4458 TAMU, College Station, Texas 77843, USA
  27. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
  28. 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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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.

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