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Reconstructing Ancestral Vertebrate Genomes by in silico Palaeogenomics

Reconstructing Ancestral Vertebrate Genomes by in silico Palaeogenomics . NB: This version only contains a subset of the slides presented at the course. Hugues Roest Crollius Laboratoire Dyogen - CNRS Ecole Normale Supérieure Paris. Bioinformatics Course Pasteur Institute

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Reconstructing Ancestral Vertebrate Genomes by in silico Palaeogenomics

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  1. Reconstructing Ancestral Vertebrate Genomes by in silico Palaeogenomics NB: This version only contains a subset of the slides presented at the course Hugues Roest Crollius Laboratoire Dyogen - CNRS Ecole Normale Supérieure Paris Bioinformatics Course Pasteur Institute Tunis, april 02 2007

  2. ancestor C C A B A B

  3. 2008 2007 100 gigabases 2006 2005 P. troglodytes C. familiaris R. norvegicus T. nigroviridis G. gallus 2004 2003 T. rubripes M. musculus 2002 H. sapiens 2001 2000 A. taliana D. melanogaster 1999 C. elegans 1998 1997 1996 S. cerevisiae H. influenzae 1995

  4. Le séquençage des génomes de vertébrés

  5. « Light » sequencing of mammal genomes (NHGRI/Broad) • And also: • Gorilla • Macaque • Pig • …

  6. Vertebrate evolution Gasterosteus aculeatus Cephalochordates (Amphioxus) Million years ago Urochordates (Ciona intestinalis) Cambrian 500 CRANIATES (-480 My) Hagfish (Myxiniformes) Ordovician Chondrichthyes (cartilaginous fish) Osteichthyes (bony fish) Silurian Paleozoic 400 Devonian Sarcopterygians Actinopterygians Tetrapodes Teleosteans Acipenseriforms (sturgeons,…) Coelacanthimorpha Carboniferous 300 Amniotes Permian Percomorphs Triassic 200 Birds Jurassic Mezozoic Cypriniforms Mammals Cretaceous Tetraodontiforms 100 Cenozoic 0 Mus musculus Homo sapiens Gallus gallus Tetraodon nigroviridis Takifugu rubripes Danio rerio

  7. Duplication of the ancestral teleost genome? zebrafish mammals Fugu scaffolds Christoffels et al. (2004) Mol. Biol. Evol.21:1146-1151 Postlethwait et al. (2000) Genome Research 10:1890-1902 Amores et al. (1998) Science 282:1711-1714

  8. whole genome duplication in teleosts duplication Homo sapiens Tetraodon nigroviridis Common ancestor diploidisation

  9. Whole Genome Duplication Duplication Diploïdisation ~800 pairs of paralogs in Tetraodon

  10. Whole Genome Duplication Gg.1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 Tetraodon chromosomes Example of Double Conserved Synteny between chicken and Tetraodon Tn.A Gg.1 Gg.1 Tn.B Gg.1 Tn.A Tn.B

  11. Whole Genome Duplication Both independent datasets (orthologs and paralogs) converge well. Gg.1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 20 Chromosomes de Tetraodon

  12. Identification of DCS blocks 6835 orthologues Chicken / Tetraodon 4299 in 517 DCS = 8.3 genes per DCS This can be repeated between chicken and each of the 4 other fish genome

  13. blocks 3 Gene loss Identifying strict synteny blocks • Series of « ultra conserved » tetrapod syntenic blocks: • same chromosome • Same order • Same orientation • No insertion / deletion Each pair of genome is « scanned » for overlapping blocks block 1 block 2

  14. Independent validation with cytogenetic data • In silico method: • 2n = 44 • Fusion 10p - 12a not seen • (but weak in cytogenetic data) • Fusion 16q - 19q not seen; visible in cow and mouse but not strong enough. • New fusion 5 + 19p • (weak, disappears if no Oppossum) • New fusion 2p + 9q (Strongly supported) Froenicke et al.,Genome Research 2006 16:306-310 > 80 Zoo-FISH comparison between mammals and human

  15. The 2R hypothesis « It is likely that the first vertebrate to emerge on this earth [had a genome] which was probably derived from a primitive chordate by tetraploidization » S. Ohno et al. (1968) Heredity 59(1):169-187 « An ancient crossopterygian fish, which served as direct ancestor of mammals, already attained the characteristic DNA content [of mammals] by a secondtetraploidisation before coming on land to live» S. Ohno et al. (1968) Heredity 59(1):169-187 Susumu Ohno 1928-2002 « Yet it is our contention that either at the fish stage or at the amphibian stage, the mammalian ancestor went through at least one tetraploid evolution» S. Ohno. (1970) Evolution by Gene Duplication p. 102. Springer-Verlag Ed. New-York Inc.

  16. http://www.biologie.ens.fr/dyogen Matthieu Muffato Hugues Roest Crollius • Collaborators: • O. Jaillon, J-M. Aury, J. Weissenbach et coll. Genoscope • The Ensembl group www.ensembl.org • M. Robinson Rechavi, R. Studer, Université de Lausanne

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