title: The genomic basis of circadian and circalunar timing adaptations in a midge.
abstract: Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes. The region most strongly associated with circadian chronotypes generates strain-specific differences in the abundance of calcium/calmodulin-dependent kinase II.1 (CaMKII.1) splice variants. As equivalent variants were shown to alter CaMKII activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma-CYCLE, we suggest that modulation of alternative splicing is a mechanism for natural adaptation in circadian timing.
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.|Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.|Research Platform 'Rhythms of Life', University of Vienna, A-1030 Vienna, Austria.
authors.forename: Tobias S
authors.initials: TS
authors.lastname: Kaiser
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.|Research Platform 'Rhythms of Life', University of Vienna, A-1030 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Poehn
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Szkiba
authors.affiliation: Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, FU Berlin, D-14195 Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Preussner
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
authors.forename: Fritz J
authors.initials: FJ
authors.lastname: Sedlazeck
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zrim
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.|Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Neumann
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.|Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, A-1030 Vienna, Austria.
authors.forename: Lam-Tung
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Institute of Population Genetics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Josef-Baumann-Gasse 1, A-1210 Vienna, Austria.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Betancourt
authors.affiliation: Research Platform 'Rhythms of Life', University of Vienna, A-1030 Vienna, Austria.|Department of Neurobiology, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
authors.affiliation: Department of Entomology, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, D-07745 Jena, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.
authors.forename: Silke
authors.initials: S
authors.lastname: Dorner
authors.affiliation: Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, FU Berlin, D-14195 Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Heyd
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna and Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.|Research Platform 'Rhythms of Life', University of Vienna, A-1030 Vienna, Austria.|Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, A-1030 Vienna, Austria.
authors.forename: Arndt
authors.initials: A
authors.lastname: von Haeseler
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.|Research Platform 'Rhythms of Life', University of Vienna, A-1030 Vienna, Austria.
authors.forename: Kristin
authors.initials: K
authors.lastname: Tessmar-Raible
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002683:Chironomidae / Q000145:classification / Q000235:genetics* / Q000502:physiology; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D056726:Genetic Association Studies; D014644:Genetic Variation; D049750:Genome, Insect / Q000235:genetics*; D023281:Genomics; D008297:Male; D016081:Moon; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D055871:Tidal Waves; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D056926:CLOCK Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2