Adam M. Session^1,2*, Yoshinobu Uno^3*, Taejoon Kwon^4,5*, Jarrod A. Chapman², Atsushi Toyoda⁶, Shuji Takahashi⁷, Akimasa Fukui⁸, Akira Hikosaka⁹, Atsushi Suzuki⁷, Mariko Kondo¹⁰, Simon J. van Heeringen¹¹, Ian Quigley¹², Sven Heinz¹³, Hajime Ogino¹⁴, Haruki Ochi¹⁵, Uffe Hellsten², Jessica B. Lyons¹, Oleg Simakov¹⁶, Nicholas Putnam¹⁷, Jonathan Stites¹⁷, Yoko Kuroki¹⁸, Toshiaki Tanaka¹⁹, Tatsuo Michiue²⁰, Minoru Watanabe²¹, Ozren B ogdanovic²², Ryan Lister²², Georgios Georgiou¹¹, Sarita S. Paranjpe¹¹, Ila van Kruijsbergen¹¹, Shengquiang Shu², Joseph Carlson², Tsutomu Kinoshita²³, Yuko Ohta²⁴, Shuuji Mawaribuchi²⁵, Jerry Jenkins^2,26, Jane Grimwood^2,26, Jeremy Schmutz^2,26, Therese Mitros¹, Sahar V. Mozaffari²⁷, Yutaka Suzuki²⁸, Yoshikazu Haramoto²⁹, Takamasa S. Yamamoto³⁰, Chiyo Takagi³⁰, Rebecca Heald³¹, Kelly Miller³¹, Christian Haudenschild^32†, Jacob Kitzman³³, Takuya Nakayama³⁴, Yumi Izutsu³⁵, Jacques Robert³⁶, Joshua Fortriede³⁷, Kevin Burns³⁷, Vaneet Lotay³⁸, Kamran Karimi³⁸, Yuuri Yasuoka³⁹, Darwin S. Dichmann¹, Martin F. Flajnik²⁴, Douglas W. Houston⁴⁰, Jay Shendure³³, Louis DuPasquier⁴¹, Peter D. Vize³⁸, Aaron M. Zorn³⁷, Michihiko Ito⁴², Edward M. Marcotte⁴, John B. Wallingford⁴, Yuzuru Ito²⁹, Makoto Asashima²⁹, Naoto Ueno^30,43, Yoichi Matsuda³, Gert Jan C. Veenstra¹¹, Asao Fujiyama^6,44,45, Richard M. Harland¹, Masanori Taira⁴⁶ & Daniel S. Rokhsar<sup>1,2,16

1</sup>University of California, Berkeley, Department of Molecular and Cell Biology and Center for Integrative Genomics, Life Sciences Addition #3200, Berkeley, California 94720-3200, USA. ²US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA. ³Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan. ⁴Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas 78712, USA. ⁵Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea. ⁶Center for Information Biology, and Advanced Genomics Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan. ⁷Amphibian Research Center, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan. ⁸Laboratory of Tissue and Polymer Sciences, Faculty of Advanced Life Science, Hokkaido University, N10W8, Kita-ku, Sapporo 060-0810, Japan. ⁹Division of Human Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521, Japan. ¹⁰Misaki Marine Biological Station (MMBS), Graduate School of Science, The University of Tokyo, 1024 Koajiro, Misaki, Miura, Kanagawa 238-0225, Japan. ¹¹Radboud University, Faculty of Science, Department of Molecular Developmental Biology, 259 RIMLS, M850/2.97, Geert Grooteplein 28, Nijmegen 6525 GA, the Netherlands. ¹²Salk Institute, Molecular Neurobiology Laboratory, La Jolla, San Diego, California 92037, USA. ¹³Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, San Diego, California 92037, USA. ¹⁴Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan. ¹⁵Institute for Promotion of Medical Science Research, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, Yamagata 990-9585, Japan. ¹⁶Molecular Genetics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan. ¹⁷Dovetail Genomics LLC. Santa Cruz, California 95060, USA. ¹⁸Department of Genome Medicine, National Research Institute for Child Health and Development, NCCHD, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan. ¹⁹Department of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. ²⁰Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo 153-8902, Japan. ²¹Institute of Institution of Liberal Arts and Fundamental Education, Tokushima University, 1-1 Minamijosanjima-cho, Tokushima 770-8502, Japan. ²²Harry Perkins Institute of Medical Research and ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Perth, Western Australia 6009, Australia. ²³Department of Life Science, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan. ²⁴Department of Microbiology and Immunology, University of Maryland, 655 W Baltimore St, Baltimore, Maryland 21201, USA. ²⁵Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane Minato-ku, Tokyo 108-8641, Japan. ²⁶HudsonAlpha Institute of Biotechnology, Huntsville, Alabama 35806, USA. ²⁷Department of Human Genetics, University of Chicago, 920 E. 58th St, CLSC 431F, Chicago, Illinois 60637, USA. ²⁸Department of Computational Biology and Medical Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwashi, Chiba 277-8568, Japan. ²⁹Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. ³⁰Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. ³¹University of California, Berkeley, Department of Molecular and Cell Biology, Life Sciences Addition #3200, Berkeley California 94720-3200, USA. ³²Illumina Inc., 25861 Industrial Blvd, Hayward, California 94545, USA. ³³Department of Genome Sciences, University of Washington, Foege Building S-250, Box 355065, 3720 15th Ave NE, Seattle Washington 98195-5065, USA. ³⁴Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA. ³⁵Department of Biology, Faculty of Science, Niigata University, 8050, Ikarashi 2-no-cho, Nishi-ku, Niigata 950-2181, Japan. ³⁶Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA. ³⁷Division of Developmental Biology, Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229-3039, USA. ³⁸Department of Biological Sciences, University of Calgary, Alberta T2N 1N4, Canada. ³⁹Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onnason, Okinawa 904-0495, Japan. ⁴⁰The University of Iowa, Department of Biology, 257 Biology Building, Iowa City, Iowa 52242-1324, USA. ⁴¹Department of Zoology and Evolutionary Biology, University of Basel, Basel CH-4051, Switzerland. ⁴²Department of Biological Sciences, School of Science, Kitasato University, 1-15-1 Minamiku, Sagamihara, Kanagawa 252-0373, Japan. ⁴³Department of Basic Biology, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. ⁴⁴Principles of Informatics, National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan. ⁴⁵Department of Genetics, SOKENDAI (The Graduate University for Advanced Studies), 1111 Yata, Mishima, Shizoka 411-8540, Japan. ⁴⁶Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ^†Present address: Personalis Inc., 1330 O’Brien Drive, Menlo Park, California 94025, USA.

^*These authors contributed equally to this work.
Corresponding authors : Richard M. Harland, Masanori Taira, Daniel S. Rokhsar

Abstract
To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ‘fossil’ transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.