Braasch I1, Gehrke AR2, Smith JJ3, Kawasaki K4, Manousaki T5, Pasquier J6, Amores A1, Desvignes T1, Batzel P1, Catchen J7, Berlin AM8, Campbell MS9, Barrell D10, Martin KJ11, Mulley JF12, Vydianathan Ravi13, Alison P. Lee13, Nakamura T2, Chalopin D14, Fan S15, Wcisel D16, Cañestro C17, Sydes J1, Beaudry FEG18, Sun Y19, Hertel J20, Beam MJ1, Fasold M20, Ishiyama M21, Johnson J8, Kehr S20, Lara M8, Letaw JH1, Litman GW22, Litman RT22, Mikami M23, Ota T24, Saha NR25, Williams L8, Stadler PF20, Wang H19, Taylor JS18, Fontenot Q26, Ferrara A26, Searle SMJ10, Aken B10, Yandell M9, Schneider I27, Yoder JA16, Volff J-N14, Meyer A15, Amemiya CT25, Byrappa Venkatesh13, Holland PWH11, Guiguen Y6, Bobe J6, Shubin NH2, Di Palma F8, Alföldi J8, Lindblad-Toh K8 & Postlethwait JH1..
1 Institute of Neuroscience, University of Oregon, Eugene, Oregon, USA.
2 Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois, USA.
3 Department of Biology, University of Kentucky, Lexington, Kentucky, USA.
4 Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania, USA.
5 Institute of Marine Biology, Biotechnology and Aquaculture, Hellenic Centre for Marine Research, Heraklion, Greece.
6 Institut National de la Recherche Agronomique (INRA), UR1037 Laboratoire de Physiologie et Génomique des Poissons (LPGP), Campus de Beaulieu, Rennes, France.
7 Department of Animal Biology, University of Illinois, Urbana-Champaign, Illinois, USA.
8 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
9 Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
10 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
11 Department of Zoology, University of Oxford, Oxford, UK.
12 School of Biological Sciences, Bangor University, Bangor, UK.
13 Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.
14 Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France.
15 Department of Biology, University of Konstanz, Konstanz, Germany.
16 Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
17 Departament de Genètica, Universitat de Barcelona, Barcelona, Spain.
18 Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
19 Center for Circadian Clocks, Soochow University, Suzhou, China.
20 Bioinformatics Group, Department of Computer Science, Universität Leipzig, Leipzig, Germany.
21 Department of Dental Hygiene, Nippon Dental University College at Niigata, Niigata, Japan.
22 Department of Pediatrics, University of South Florida Morsani College of Medicine, St. Petersburg, Florida, USA.
23 Department of Microbiology, Nippon Dental University School of Life Dentistry at Niigata, Niigata, Japan.
24 Department of Evolutionary Studies of Biosystems, SOKENDAI (Graduate University for Advanced Studies), Hayama, Japan.
25 Molecular Genetics Program, Benaroya Research Institute, Seattle, Washington, USA.
26 Department of Biological Sciences, Nicholls State University, Thibodaux, Louisiana, USA.
27 Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem, Brazil.
Published online in Nature Genetics on 7 Mar 2016.
To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
Figure: Gar provides connectivity of vertebrate regulatory elements. (A) The ‘gar bridge’ principle of vertebrate CNE connectivity from human through gar to teleosts. Hidden orthology is uncovered for elements that do not directly align between human and teleosts but become evident when first aligning tetrapod genomes to gar, and then aligning gar and teleost genomes. (B) Connectivity analysis of 13-way whole-genome alignments shows the evolutionary gain (green) and loss (red) of 153 human limb enhancers. Direct human-teleost orthology could only be established for 81 elements as opposed to 95 when using gar as a bridge as in (A).
For more information on Byrappa VENKATESH 's lab, please click here.