title: Using the canary genome to decipher the evolution of hormone-sensitive gene regulation in seasonal singing birds.
abstract: BACKGROUND
  While the song of all songbirds is controlled by the same neural circuit, the hormone dependence of singing behavior varies greatly between species. For this reason, songbirds are ideal organisms to study ultimate and proximate mechanisms of hormone-dependent behavior and neuronal plasticity.
  
  
  RESULTS
  We present the high quality assembly and annotation of a female 1.2-Gbp canary genome. Whole genome alignments between the canary and 13 genomes throughout the bird taxa show a much-conserved synteny, whereas at the single-base resolution there are considerable species differences. These differences impact small sequence motifs like transcription factor binding sites such as estrogen response elements and androgen response elements. To relate these species-specific response elements to the hormone-sensitivity of the canary singing behavior, we identify seasonal testosterone-sensitive transcriptomes of major song-related brain regions, HVC and RA, and find the seasonal gene networks related to neuronal differentiation only in the HVC. Testosterone-sensitive up-regulated gene networks of HVC of singing males concerned neuronal differentiation. Among the testosterone-regulated genes of canary HVC, 20% lack estrogen response elements and 4 to 8% lack androgen response elements in orthologous promoters in the zebra finch.
  
  
  CONCLUSIONS
  The canary genome sequence and complementary expression analysis reveal intra-regional evolutionary changes in a multi-regional neural circuit controlling seasonal singing behavior and identify gene evolution related to the hormone-sensitivity of this seasonal singing behavior. Such genes that are testosterone- and estrogen-sensitive specifically in the canary and that are involved in rewiring of neurons might be crucial for seasonal re-differentiation of HVC underlying seasonal song patterning.
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. frankl@orn.mpg.de.
authors: Carolina
authors: C
authors: Frankl-Vilches
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. kuhl@molgen.mpg.de.|Max Planck Institute for Molecular Genetics, Sequencing Core Facility, 14195, Berlin, Germany. kuhl@molgen.mpg.de.
authors: Heiner
authors: H
authors: Kuhl
authors: Max Planck Institute for Molecular Genetics, Sequencing Core Facility, 14195, Berlin, Germany. werber@molgen.mpg.de.
authors: Martin
authors: M
authors: Werber
authors: Max Planck Institute for Molecular Genetics, Sequencing Core Facility, 14195, Berlin, Germany. klages@molgen.mpg.de.
authors: Sven
authors: S
authors: Klages
authors: Max Planck Institute for Molecular Genetics, Sequencing Core Facility, 14195, Berlin, Germany. mkerick@molgen.mpg.de.
authors: Martin
authors: M
authors: Kerick
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. bakker@orn.mpg.de.
authors: Antje
authors: A
authors: Bakker
authors: Laboratório de Cultura de Tecidos e Citogenética, SAMAM, Instituto Evandro Chagas, Ananindeua, Pará, and Faculdade de Ciências Naturais (ICEN), Universidade Federal do Pará, Belém, 66075-110, Brazil. ehco@ufpa.br.
authors: Edivaldo Hc
authors: EH
authors: de Oliveira
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. creusch@orn.mpg.de.
authors: Christina
authors: C
authors: Reusch
authors: Department of Biochemistry and Cambridge Systems Biology Centre, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. fc301@cam.ac.uk.
authors: Floriana
authors: F
authors: Capuano
authors: Department of Biochemistry and Cambridge Systems Biology Centre, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. jv330@cam.ac.uk.
authors: Jakob
authors: J
authors: Vowinckel
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. leitner@orn.mpg.de.
authors: Stefan
authors: S
authors: Leitner
authors: Department of Biochemistry and Cambridge Systems Biology Centre, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. mr559@cam.ac.uk.|Division of Physiology and Metabolism, MRC National Institute for Medical Research, the Ridgeway, Mill Hill, London, NW7 1AA, UK. mr559@cam.ac.uk.
authors: Markus
authors: M
authors: Ralser
authors: Max Planck Institute for Molecular Genetics, Sequencing Core Facility, 14195, Berlin, Germany. timmerma@molgen.mpg.de.
authors: Bernd
authors: B
authors: Timmermann
authors: Department of Behavioral Neurobiology, Max Planck Institute for Ornithology, 82319, Seewiesen, Germany. gahr@orn.mpg.de.
authors: Manfred
authors: M
authors: Gahr
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002171:Canaries / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000187:drug effects; D016678:Genome; D006728:Hormones / Q000494:pharmacology*; D017403:In Situ Hybridization; D007621:Karyotyping; D008297:Male; D058977:Molecular Sequence Annotation; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012621:Seasons; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D013739:Testosterone / Q000494:pharmacology; D059467:Transcriptome / Q000235:genetics; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D006728:Hormones; D020543:Proteome; D012333:RNA, Messenger; D013739:Testosterone
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