Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock

Rubin, Elad B.; Shemesh, Yair; Cohen, Mira; Elgavish, Sharona; Robertson, Hugh M.; Bloch, Guy

doi:10.1101/gr.5094806

PreprintCited by 257Circadian rhythm and melatoninInsect and Arachnid Ecology and BehaviorNeurobiology and Insect Physiology Research

Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock

Open access

Rubin, Elad B., Shemesh, Yair, Cohen, Mira, Elgavish, Sharona, Robertson, Hugh M., Bloch, Guy·2006·Genome Research

DOI 10.1101/gr.5094806PMC PMC1626637

Open this paper in CoChat — free account Open PDF

Abstract

The circadian clock of the honey bee is implicated in ecologically relevant complex behaviors. These include time sensing, time-compensated sun-compass navigation, and social behaviors such as coordination of activity, dance language communication, and division of labor. The molecular underpinnings of the bee circadian clock are largely unknown. We show that clock gene structure and expression pattern in the honey bee are more similar to the mouse than to Drosophila. The honey bee genome does not encode an ortholog of Drosophila Timeless (Tim1), has only the mammalian type Cryptochrome (Cry-m), and has a single ortholog for each of the other canonical "clock genes." In foragers that typically have strong circadian rhythms, brain mRNA levels of amCry, but not amTim as in Drosophila, consistently oscillate with strong amplitude and a phase similar to amPeriod (amPer) under both light-dark and constant darkness illumination regimes. In contrast to Drosophila, the honey bee amCYC protein contains a transactivation domain and its brain transcript levels oscillate at virtually an anti-phase to amPer, as it does in the mouse. Phylogenetic analyses indicate that the basal insect lineage had both the mammalian and Drosophila types of Cry and Tim. Our results suggest that during evolution, Drosophila diverged from the ancestral insect clock and specialized in using a set of clock gene orthologs that was lost by both mammals and bees, which in turn converged and specialized in the other set. These findings illustrate a previously unappreciated diversity of insect clockwork and raise critical questions concerning the evolution and functional significance of species-specific variation in molecular clockwork.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1101/gr.5094806

Cites

117 of 117 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Three ancient bilaterian cryptochrome families have been reported in the sea urchin.
“has also been reported to contain three ancient bilaterian families of Cryptochromes (Rubin et al., 2006).”
From Opsins and clusters of sensory G-protein-coupled receptors in the sea urchin genome (2006) · cites this paper as Rubin et al., 2006

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice
Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.22.4673 · Cited by 64,617 · see citing works
The Pfam Protein Families Database
Bateman, A. G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.276 · Cited by 14,062 · see citing works
EMBOSS: the European molecular biology open software suite.
Rice, P., Longden, I., & Bleasby, A. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)02024-2 · Cited by 9,466 · see citing works
SMART, a simple modular architecture research tool: Identification of signaling domains
Schultz, J., Milpetz, F., Peer Bork, B., & Ponting, C. P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.5857 · Cited by 3,577 · see citing works
The Pfam protein families database
Bateman, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh121 · Cited by 3,127 · see citing works
Molecular Bases for Circadian Clocks
Dunlap, J. C. (1999) · Cell · doi:10.1016/s0092-8674(00)80566-8 · Cited by 2,900 · see citing works
Multiple sequence alignment with Clustal X
Jeanmougin, F., Thompson, J. D., Gouy, M., Higgins, D. G., & Gibson, T. J. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01285-7 · Cited by 2,652 · see citing works
The Dance Language and Orientation of Bees
von Frisch, K. (1993) · Harvard University Press eBooks · doi:10.4159/harvard.9780674418776 · Cited by 2,598 · see citing works
TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing
Schmidt, H. A., Strimmer, K., Vingron, M., & von Haeseler, A. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.3.502 · Cited by 2,512 · see citing works
Insights into social insects from the genome of the honeybee Apis mellifera
Weinstock, G. M., Gibbs, R. A., Worley, K. C., Sodergren, E. J., Milosavljević, A., Richards, S., Miller, J., Jiang, H., Zhang, L., Wei, X., et al. (2006) · Nature · doi:10.1038/nature05260 · Cited by 1,871 · see citing works
Self-citation
mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop
Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)81014-4 · Cited by 1,617 · see citing works
Circadian rhythms from multiple oscillators: lessons from diverse organisms
Bell‐Pedersen, D., Cassone, V. M., Earnest, D. J., Golden, S. S., Hardin, P. E., Thomas, T. L., & Zoran, M. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1633 · Cited by 1,481 · see citing works
Enhanced genome annotation using structural profiles in the program 3D-PSSM 1 1Edited by J. Thornton
Kelley, L. A., MacCallum, R. M., & Sternberg, M. J. E. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3741 · Cited by 1,462 · see citing works
Molecular analysis of mammalian circadian rhythms
Reppert, S. M., & Weaver, D. R. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.647 · Cited by 1,444 · see citing works
Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms
Horst, G. T. J. V. D., Muijtjens, M., Kobayashi, K., Takano, R., Kanno, S.-I., Takao, M., Wit, J. D., Verkerk, A., Eker, A. P. M., Leenen, D. V., et al. (1999) · Nature · doi:10.1038/19323 · Cited by 1,402 · see citing works
Development and Validation of Real-Time Quantitative Reverse Transcriptase–Polymerase Chain Reaction for Monitoring Gene Expression in Cardiac Myocytesin Vitro
Winer, J., Jung, C. K. S., Shackel, I., & Williams, P. M. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4085 · Cited by 1,388 · see citing works
Positional Cloning of the Mouse Circadian Gene
King, D. P., Zhao, Y., Sangoram, A. M., Wilsbacher, L. D., Tanaka, M., Antoch, M. P., Steeves, T. D. L., Vitaterna, M. H., Kornhauser, J. M., Lowrey, P. L., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80245-7 · Cited by 1,382 · see citing works
The genome of the social amoeba Dictyostelium discoideum
Eichinger, L., Pachebat, J. A., Glöckner, G., Rajandream, M.-A., Sucgang, R., Berriman, M., Song, J., Olsen, R., Szafranski, K., Xu, Q., et al. (2005) · Nature · doi:10.1038/nature03481 · Cited by 1,351 · see citing works
Structure and Function of DNA Photolyase and Cryptochrome Blue-Light Photoreceptors
Sancar, A. (2003) · Chemical Reviews · doi:10.1021/cr0204348 · Cited by 1,290 · see citing works
CDD: a Conserved Domain Database for protein classification
Marchler-Bauer, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki069 · Cited by 1,156 · see citing works
Time zones: a comparative genetics of circadian clocks
Young, M. W., & Kay, S. A. (2001) · Nature Reviews Genetics · doi:10.1038/35088576 · Cited by 1,143 · see citing works
A Draft Sequence for the Genome of the Domesticated Silkworm ( Bombyx mori )
Biology analysis group, Xia, Q., Zhou, Z., Lu, C., Cheng, D., Dai, F., Li, B., Zhao, P., Zha, X., Cheng, T., et al. (2004) · Science · doi:10.1126/science.1102210 · Cited by 1,121 · see citing works
Circadian rhythms from flies to human
Panda, S., Hogenesch, J. B., & Kay, S. A. (2002) · Nature · doi:10.1038/417329a · Cited by 1,044 · see citing works
Cryptochromes: Blue Light Receptors for Plants and Animals
Cashmore, A. R., Jarillo, J. A., Wu, Y., & Liu, D. (1999) · Science · doi:10.1126/science.284.5415.760 · Cited by 1,027 · see citing works
SMART 4.0: towards genomic data integration
Letunić, I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh088 · Cited by 997 · see citing works
The PROSITE database
Hulo, N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj063 · Cited by 971 · see citing works
CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity
Emery, P., So, W. V., Kaneko, M., Hall, J. C., & Rosbash, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81637-2 · Cited by 912 · see citing works
GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences
Jones, D. T. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2583 · Cited by 888 · see citing works
Closing the Circadian Loop: CLOCK-Induced Transcription of Its Own Inhibitors per and tim
Darlington, T. K., Wager‐Smith, K., Ceriani, M. F., Staknis, D., Gekakis, N., Steeves, T. D. L., Weitz, C. J., Takahashi, J. S., & Kay, S. A. (1998) · Science · doi:10.1126/science.280.5369.1599 · Cited by 826 · see citing works
A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless
Allada, R., White, N. E., So, W. V., Hall, J. C., & Rosbash, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81440-3 · Cited by 744 · see citing works
Differential regulation of mammalian <i>Period</i> genes and circadian rhythmicity by cryptochromes 1 and 2
Vitaterna, M. H., Selby, C. P., Todo, T., Niwa, H., Thompson, C., Fruechte, E. M., Hitomi, K., Thresher, R. J., Ishikawa, T., Miyazaki, J., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.12114 · Cited by 690 · see citing works
The Genome Sequence of Silkworm, Bombyx mori
Mita, K. (2004) · DNA Research · doi:10.1093/dnares/11.1.27 · Cited by 659 · see citing works
Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock
Griffin, E. A., Staknis, D., & Weitz, C. J. (1999) · Science · doi:10.1126/science.286.5440.768 · Cited by 646 · see citing works
CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless
Rutila, J. E., Suri, V., Le, M., So, W. V., Rosbash, M., & Hall, J. C. (1998) · Cell · doi:10.1016/s0092-8674(00)81441-5 · Cited by 643 · see citing works
Light-Dependent Sequestration of TIMELESS by CRYPTOCHROME
Ceriani, M. F., Darlington, T. K., Staknis, D., Más, P., Petti, A. A., Weitz, C. J., & Kay, S. A. (1999) · Science · doi:10.1126/science.285.5427.553 · Cited by 565 · see citing works
vrille, Pdp1, and dClock Form a Second Feedback Loop in the Drosophila Circadian Clock
Cyran, S. A., Buchsbaum, A. M., Reddy, K. L., Lin, M.-C., Glossop, N. R. J., Hardin, P. E., Young, M. W., Storti, R. V., & Blau, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00074-6 · Cited by 549 · see citing works
Comparative genome sequencing of Drosophila pseudoobscura : Chromosomal, gene, and cis -element evolutionPreprint
Richards, S., Liu, Y., Bettencourt, B. R., Hradecky, P., Letovsky, S., Nielsen, R., Thornton, K., Hubisz, M. J., Chen, R., Meisel, R. P., et al. (2005) · Genome Research · doi:10.1101/gr.3059305 · Cited by 498 · see citing works
The Circadian Timekeeping System of Drosophila
Hardin, P. E. (2005) · Current Biology · doi:10.1016/j.cub.2005.08.019 · Cited by 474 · see citing works
GenBank
Benson, D. A. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.17 · Cited by 456 · see citing works
An Insect Molecular Clock Dates the Origin of the Insects and Accords with Palaeontological and Biogeographic Landmarks
Gaunt, M. W., & Miles, M. A. (2002) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a004133 · Cited by 435 · see citing works
FlyBase: genes and gene models
Drysdale, R. A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki046 · Cited by 381 · see citing works
Isolation of timeless by PER Protein Interaction: Defective Interaction Between timeless Protein and Long-Period Mutant PER L
Gekakis, N., Sáez, L., Delahaye-Brown, A.-M., Myers, M. P., Sehgal, A., Young, M. W., & Weitz, C. J. (1995) · Science · doi:10.1126/science.270.5237.811 · Cited by 371 · see citing works
The Clocks That Time Us: Physiology of the Circadian Timing System
(1983) · Journal of Gerontology · doi:10.1093/geronj/38.2.246a · Cited by 349 · see citing works
Improvement of the GenTHREADER method for genomic fold recognition
McGuffin, L. J., & Jones, D. T. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg097 · Cited by 345 · see citing works
Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms
Field, M. D., Maywood, E. S., O'Brien, J. A., Weaver, D. R., Reppert, S. M., & Hastings, M. H. (2000) · Neuron · doi:10.1016/s0896-6273(00)80906-x · Cited by 343 · see citing works
Regulation of Nuclear Entry of the Drosophila Clock Proteins Period and Timeless
Sáez, L., & Young, M. W. (1996) · Neuron · doi:10.1016/s0896-6273(00)80222-6 · Cited by 330 · see citing works
Cryptochromes
Cashmore, A. R. (2003) · Cell · doi:10.1016/s0092-8674(03)00647-0 · Cited by 312 · see citing works
Roles of the Two Drosophila CRYPTOCHROME Structural Domains in Circadian Photoreception
Busza, A. C., Emery-Le, M., Rosbash, M., & Emery, P. (2004) · Science · doi:10.1126/science.1096973 · Cited by 292 · see citing works
VRILLE Feeds Back to Control Circadian Transcription of Clock in the Drosophila Circadian Oscillator
Glossop, N. R. J., Houl, J. H., Zheng, H., Ng, F., DUDEK, S. M., & Hardin, P. E. (2003) · Neuron · doi:10.1016/s0896-6273(03)00002-3 · Cited by 286 · see citing works
Circadian rhythms in a nutshell
Edery, I. (2000) · Physiological Genomics · doi:10.1152/physiolgenomics.2000.3.2.59 · Cited by 284 · see citing works
Human and mouse oligonucleotide-based array CGH
van den IJssel, P. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni191 · Cited by 274 · see citing works
PER and TIM Inhibit the DNA Binding Activity of a Drosophila CLOCK-CYC/dBMAL1 Heterodimer without Disrupting Formation of the Heterodimer: a Basis for Circadian Transcription
Lee, C., Bae, K., & Edery, I. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.8.5316 · Cited by 242 · see citing works
A new role for cryptochrome in a Drosophila circadian oscillator
Krishnan, B., Levine, J. D., Lynch, M. K. S., Dowse, H. B., Funes, P., Hall, J. C., Hardin, P. E., & Dryer, S. E. (2001) · Nature · doi:10.1038/35077094 · Cited by 239 · see citing works
The two CRYs of the butterfly
Zhu, H., Yuan, Q., Froy, O., Casselman, A., & Reppert, S. M. (2005) · Current Biology · doi:10.1016/j.cub.2005.11.030 · Cited by 238 · see citing works
Circadian Clock Neurons in the Silkmoth Antheraea pernyi: Novel Mechanisms of Period Protein Regulation
Šauman, I., & Reppert, S. M. (1996) · Neuron · doi:10.1016/s0896-6273(00)80220-2 · Cited by 238 · see citing works
Genetic analysis of the circadian system in Drosophila melanogaster and mammals
Stanewsky, R. (2002) · Journal of Neurobiology · doi:10.1002/neu.10164 · Cited by 219 · see citing works
Organization of the Circadian System in Insects
Helfrich‐Förster, C., Stengl, M., & Homberg, U. (1998) · Chronobiology International · doi:10.3109/07420529808993195 · Cited by 217 · see citing works
Molecular analysis of avian circadian clock genes
Yoshimura, T., Suzuki, Y., Makino, E., Suzuki, T., Kuroiwa, A., Matsuda, Y., NAMIKAWA, T., & Ebihara, S. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00091-7 · Cited by 211 · see citing works
Molecular Components of the Circadian System in Drosophila
Williams, J. A., & Sehgal, A. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.729 · Cited by 211 · see citing works
Molecular analysis of zebrafish photolyase/cryptochrome family: two types of cryptochromes present in zebrafish
Kobayashi, Y., Ishikawa, T., Hirayama, J., Daiyasu, H., Kanai, S., Toh, H., Fukuda, I., Tsujimura, T., Terada, N., Kamei, Y., et al. (2000) · Genes to Cells · doi:10.1046/j.1365-2443.2000.00364.x · Cited by 208 · see citing works
Requirement of Mammalian Timeless for Circadian Rhythmicity
Barnes, J. W., Tischkau, S. A., Barnes, J. A., Mitchell, J. W., Burgoon, P. W., Hickok, J. R., & Gillette, M. U. (2003) · Science · doi:10.1126/science.1086593 · Cited by 207 · see citing works
Connecting the Navigational Clock to Sun Compass Input in Monarch Butterfly Brain
Šauman, I., Briscoe, A. D., Zhu, H., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.014 · Cited by 202 · see citing works
Transcriptional Repression by a Novel Member of the bZIP Family of Transcription Factors
Cowell, I. G., Skinner, A., & Hurst, H. C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.7.3070 · Cited by 192 · see citing works
Role of Structural Plasticity in Signal Transduction by the Cryptochrome Blue-Light Photoreceptor
Partch, C. L., Clarkson, M. W., Özgür, S., Lee, A. L., & Sancar, A. (2005) · Biochemistry · doi:10.1021/bi047545g · Cited by 188 · see citing works
A time-less function for mouse Timeless
Gotter, A. L., Manganaro, T. F., Weaver, D. R., Kolakowski, L. F., Possidente, B. P., Sathyanarayanan, S., MacLaughlin, D. T., & Reppert, S. M. (2000) · Nature Neuroscience · doi:10.1038/77653 · Cited by 179 · see citing works
Changes in period mRNA levels in the brain and division of labor in honey bee colonies
Toma, D. P., Bloch, G., Moore, D., & Robinson, G. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.12.6914 · Cited by 170 · see citing works
Self-citation
Molecular Analysis of Mammalian Timeless
Zylka, M. J., Shearman, L. P., Levine, J. D., Jin, X., Weaver, D. R., & Reppert, S. M. (1998) · Neuron · doi:10.1016/s0896-6273(00)80628-5 · Cited by 169 · see citing works
Honey bee circadian clocks: behavioral control from individual workers to whole-colony rhythms
Moore, D. (2001) · Journal of Insect Physiology · doi:10.1016/s0022-1910(01)00057-9 · Cited by 168 · see citing works
Circadian Photoreception in Drosophila : Functions of Cryptochrome in Peripheral and Central Clocks
Ivanchenko, M. G., Stanewsky, R., & Giebultowicz, J. M. (2001) · Journal of Biological Rhythms · doi:10.1177/074873040101600303 · Cited by 159 · see citing works
Pteropsin: A vertebrate-like non-visual opsin expressed in the honey bee brain
Velarde, R. A., Sauer, C. D., Walden, K. K. O., Fahrbach, S. E., & Robertson, H. M. (2005) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2005.09.001 · Cited by 156 · see citing works
Self-citation
Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY
Rosato, E., Codd, V., Mazzotta, G. M., Piccin, A., Zordan, M. A., Costa, R., & Kyriacou, C. P. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00259-7 · Cited by 151 · see citing works
Behavioral Rhythmicity, Age, Division of Labor and period Expression in the Honey Bee Brain
Bloch, G., Toma, D. P., & Robinson, G. E. (2001) · Journal of Biological Rhythms · doi:10.1177/074873001129002123 · Cited by 150 · see citing works
Self-citation
Transcription Regulation within the Circadian Clock: The E-box and Beyond
Hardin, P. E. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730404268052 · Cited by 148 · see citing works
Timekeeping in the honey bee colony: integration of circadian rhythms and division of labor
Moore, D., Angel, J. E., Cheeseman, I. M., Fahrbach, S. E., & Robinson, G. E. (1998) · Behavioral Ecology and Sociobiology · doi:10.1007/s002650050476 · Cited by 147 · see citing works
Drosophila CRYPTOCHROME Is a Circadian Transcriptional Repressor
Collins, B. H., Mazzoni, E. O., Stanewsky, R., & Blau, J. (2006) · Current Biology · doi:10.1016/j.cub.2006.01.034 · Cited by 141 · see citing works
The Coevolution of Blue-Light Photoreception and Circadian Rhythms
Gehring, W., & Rosbash, M. (2003) · Journal of Molecular Evolution · doi:10.1007/s00239-003-0038-8 · Cited by 132 · see citing works
Short-day and long-day expression patterns of genes involved in the flesh fly clock mechanism: period, timeless, cycle and cryptochrome
Goto, S. G., & Denlinger, D. L. (2002) · Journal of Insect Physiology · doi:10.1016/s0022-1910(02)00108-7 · Cited by 128 · see citing works
A constitutively active cryptochrome in Drosophila melanogaster
Dissel, S., Codd, V., Fedič, R., Garner, K. J., Costa, R., Kyriacou, C. P., & Rosato, E. (2004) · Nature Neuroscience · doi:10.1038/nn1285 · Cited by 124 · see citing works
Reversal of honeybee behavioural rhythms
Bloch, G., & Robinson, G. E. (2001) · Nature · doi:10.1038/35074183 · Cited by 118 · see citing works
Self-citation
Identification of cryptochrome DASH from vertebrates
Daiyasu, H., Ishikawa, T., Kuma, K., Iwai, S., Todo, T., & Toh, H. (2004) · Genes to Cells · doi:10.1111/j.1356-9597.2004.00738.x · Cited by 114 · see citing works
Neuroanatomical studies of period gene expression in the hawkmoth, Manduca sexta
Wise, S. K., Davis, N. T., Tyndale, E., Noveral, J., Folwell, M. G., Bedian, V., Emery, I. F., & Siwicki, K. K. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10242 · Cited by 109 · see citing works
Functional Evolution of the Photolyase/Cryptochrome Protein Family: Importance of the C Terminus of Mammalian CRY1 for Circadian Core Oscillator Performance
Chaves, I., Yagita, K., Barnhoorn, S., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.5.1743-1753.2006 · Cited by 104 · see citing works
Distribution of PER Protein, Pigment-Dispersing Hormone, Prothoracicotropic Hormone, and Eclosion Hormone in the Cephalic Nervous System of Insects
Závodská, R., Šauman, I., & Sehnal, F. (2003) · Journal of Biological Rhythms · doi:10.1177/0748730403251711 · Cited by 102 · see citing works
Redox Potential
Froy, O., Chang, D. C., & Reppert, S. M. (2002) · Current Biology · doi:10.1016/s0960-9822(01)00656-x · Cited by 101 · see citing works
Structural and functional features of transcription factors controlling the circadian clock
Hirayama, J., & Sassone‐Corsi, P. (2005) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2005.07.003 · Cited by 101 · see citing works
Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3
Takahata, S., Ozaki, T., Mimura, J., Kikuchi, Y., Sogawa, K., & Fujii‐Kuriyama, Y. (2000) · Genes to Cells · doi:10.1046/j.1365-2443.2000.00363.x · Cited by 97 · see citing works
Advanced analysis of a cryptochrome mutation's effects on the robustness and phase of molecular cycles in isolated peripheral tissues of Drosophila
Levine, J. D., Funes, P., Dowse, H. B., & Hall, J. C. (2002) · BMC Neuroscience · doi:10.1186/1471-2202-3-5 · Cited by 94 · see citing works
Clock Gene Evolution and Functional Divergence
Tauber, E., Last, K. S., Olive, P. J. W., & Kyriacou, C. P. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730404268775 · Cited by 94 · see citing works
Structure and expressions of two circadian clock genes, period and timeless in the commercial silkmoth, Bombyx mori
Iwai, S., Fukui, Y., Fujiwara, Y., et al. (2006) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2006.03.001 · Cited by 91 · see citing works
Cryptochromes: sensory reception, transduction, and clock functions subserving circadian systems
Hall, J. C. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00117-3 · Cited by 89 · see citing works
Cloning of a marsupial DNA photolyase gene and the lack of related nucleotide sequences in placental mammals
Kato, T., Todo, T., Ayaki, H., Ishizaki, K., Morita, T., MITRA, S. P., & Ikenaga, M. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.20.4119 · Cited by 84 · see citing works
A second timeless gene in Drosophila shares greater sequence similarity with mammalian tim
Benna, C., Scannapieco, P., Piccin, A., Sandrelli, F., Zordan, M. A., Rosato, E., Kyriacou, C. P., Valle, G., & Costa, R. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00594-7 · Cited by 79 · see citing works
Patterns of PERIOD and pigment‐dispersing hormone immunoreactivity in the brain of the European honeybee (Apis mellifera): Age‐ and time‐related plasticity
Bloch, G., Solomon, S. M., Robinson, G. E., et al. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10778 · Cited by 70 · see citing works
Self-citation
A mammalian ortholog of Drosophila timeless, highly expressed in SCN and retina, forms a complex with mPER1
Takumi, T., Nagamine, Y., Miyake, S., Matsubara, C., Taguchi, K., Takekida, S., Sakakida, Y., Nishikawa, K., Kishimoto, T., Niwa, S., et al. (1999) · Genes to Cells · doi:10.1046/j.1365-2443.1999.00238.x · Cited by 69 · see citing works
Serine phosphorylation of mCRY1 and mCRY2 by mitogen‐activated protein kinase
Sanada, K., Harada, Y., Sakai, M., Todo, T., & Fukada, Y. (2004) · Genes to Cells · doi:10.1111/j.1356-9597.2004.00758.x · Cited by 69 · see citing works
Constructing a Feedback Loop with Circadian Clock Molecules from the Silkmoth, Antheraea pernyi
Chang, D. C., McWatters, H. G., Williams, J. A., Gotter, A. L., Levine, J. D., & Reppert, S. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306937200 · Cited by 67 · see citing works
Computational Tools For Protein Modeling
Xu, D. H., Xu, Y., & Uberbacher, E. C. (2000) · Current Protein and Peptide Science · doi:10.2174/1389203003381469 · Cited by 58 · see citing works
Beetling around the genome
Brown, S. J., Denell, R. E., & Beeman, R. W. (2003) · Genetics Research · doi:10.1017/s0016672303006451 · Cited by 56 · see citing works
Full sisters and super sisters: a terminological paradigm
Page, R. E., & Laidlaw, H. H. (1988) · Animal Behaviour · doi:10.1016/s0003-3472(88)80181-7 · Cited by 56 · see citing works
Molecular Cloning and Circadian Regulation of Cryptochrome Genes in Japanese Quail ( Coturnix coturnix japonica )
Fu, Z., Inaba, M., Noguchi, T., & Kato, H. (2002) · Journal of Biological Rhythms · doi:10.1177/074873002129002302 · Cited by 55 · see citing works
PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes
Lin, S., Lin, M., Horváth, P., Reddy, K. L., & Storti, R. V. (1997) · Development · doi:10.1242/dev.124.22.4685 · Cited by 55 · see citing works
Immunocytochemical distribution of pigment-dispersing hormone in the cephalic ganglia of polyneopteran insects
Sehadová, H., Šauman, I., & Sehnal, F. (2003) · Cell and Tissue Research · doi:10.1007/s00441-003-0705-5 · Cited by 54 · see citing works
Functional and Structural Analyses of Cryptochrome
Hirayama, J., Nakamura, H., Ishikawa, T., Kobayashi, Y., & Todo, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305028200 · Cited by 53 · see citing works
Self-organization of circadian rhythms in groups of honeybees (Apis mellifera L.)
Moritz, R. F. A., & Kryger, P. (1994) · Behavioral Ecology and Sociobiology · doi:10.1007/bf00167746 · Cited by 49 · see citing works
Circadian genes in a blind subterranean mammal II: Conservation and uniqueness of the three Period homologs in the blind subterranean mole rat, Spalax ehrenbergi superspecies
Avivi, A., Oster, H., Joel, A., Beiles, A., Albrecht, U., & Nevo, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182423299 · Cited by 45 · see citing works
Importin α/β Mediates Nuclear Transport of a Mammalian Circadian Clock Component, mCRY2, Together with mPER2, through a Bipartite Nuclear Localization Signal
Sakakida, Y., Miyamoto, Y., Nagoshi, E., Akashi, M., Nakamura, T. J., Mamine, T., Kasahara, M., Minami, Y., Yoneda, Y., & Takumi, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413236200 · Cited by 44 · see citing works
Flies, clocks and evolution
Rosato, E., & Kyriacou, C. P. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2001.0961 · Cited by 41 · see citing works
Nuclear Localization and Transcriptional Repression Are Confined to Separable Domains in the Circadian Protein CRYPTOCHROME
Zhu, H., Conte, F., & Green, C. B. (2003) · Current Biology · doi:10.1016/j.cub.2003.08.033 · Cited by 40 · see citing works
Circadian Genes in a Blind Subterranean Mammal III: Molecular Cloning and Circadian Regulation of Cryptochrome Genes in the Blind Subterranean Mole Rat, Spalax Ehrenbergi Superspecies
Avivi, A., Oster, H., Joel, A., Beiles, A., Albrecht, U., & Nevo, E. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730403260622 · Cited by 37 · see citing works
Transcriptional Repression by a Novel Member of the bZIP Family of Transcription Factors
Cowell, I. G., Skinner, A., & Hurst, H. C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.7.3070-3077.1992 · Cited by 33 · see citing works
period expression in the honey bee brain is developmentally regulated and not affected by light, flight experience, or colony type
Bloch, G., Rubinstein, C. D., & Robinson, G. E. (2004) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2004.05.004 · Cited by 32 · see citing works
Self-citation
Cryptochromes: Tail-ored for Distinct Functions
Green, C. B. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.040 · Cited by 24 · see citing works
The Drosophila clock protein Timeless is a member of the Arm/HEAT family
Vodovar, N., Clayton, J. D., Costa, R., Odell, M., & Kyriacou, C. P. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01130-2 · Cited by 15 · see citing works
Insect Genomes
Robertson, H. M. (2005) · American Entomologist · doi:10.1093/ae/51.3.166 · Cited by 13 · see citing works
Self-citation
Seasonal and task-related variation in free running activity rhythms in honey bees (Apis mellifera)
Bloch, G., Shemesh, Y., & Robinson, G. E. (2006) · Insectes Sociaux · doi:10.1007/s00040-005-0844-7 · Cited by 9 · see citing works
Self-citation
Weighing in on a timeless controversy
Perry, J. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20706 · Cited by 3 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Swofford, D.L. 2001. PAUP*: Phylogenetic analysis using parsimony and other methods, version 4. Sinauer Press, New York.

Sorted by citations

The cryptochromes: blue light photoreceptors in plants and animals
Chaves, I., Pokorny, R., Byrdin, M., Hoang, N., Ritz, T., Brettel, K., Essen, L.-O., van der Horst, G. T. J., Batschauer, A., & Ahmad, M. (2011) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-042110-103759 · Cited by 845 · see citing works
The evolution of eyes and visually guided behaviour
Nilsson, D.-E. (2009) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2009.0083 · Cited by 258 · see citing works
Another place, another timer: marine species and the rhythms of life
Tessmar‐Raible, K., Raible, F., & Arboleda, E. (2011) · BioEssays · doi:10.1002/bies.201000096 · Cited by 208 · see citing works
Opsins and clusters of sensory G-protein-coupled receptors in the sea urchin genome
Raible, F., Tessmar-Raible, K., Arboleda, E., Kaller, T., Bork, P., Arendt, D., & Arnone, M. I. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.070 · Cited by 170 · see citing works
The cryptochrome/photolyase family in aquatic organisms
Oliveri, P., Fortunato, A. E., Petrone, L., Ishikawa-Fujiwara, T., Kobayashi, Y., Todo, T., Antonova, O., Arboleda, E., Zantke, J., Tessmar-Raible, K., et al. (2014) · Marine Genomics · doi:10.1016/j.margen.2014.02.001 · Cited by 90 · see citing works
Lunar phase-dependent expression of cryptochrome and a photoperiodic mechanism for lunar phase-recognition in a reef fish, goldlined spinefoot
Fukushiro, M., Takeuchi, T., Takeuchi, Y., Hur, S.-P., Sugama, N., Takemura, A., Kubo, Y., Okano, K., & Okano, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028643 · Cited by 47 · see citing works

Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila 's circadian clock
Peschel, N., Veleri, S., & Stanewsky, R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606675103 · Cited by 102 · see citing works
A concise overview of circadian timing in Drosophila
Costa, R. (2003) · Frontiers in bioscience · doi:10.2741/1036 · Cited by 6 · see citing works
Light-Dependent Sequestration of TIMELESS by CRYPTOCHROME
Ceriani, M. F., Darlington, T. K., Staknis, D., Más, P., Petti, A. A., Weitz, C. J., & Kay, S. A. (1999) · Science · doi:10.1126/science.285.5427.553 · Cited by 565 · see citing works
Loss of Timeless Underlies an Evolutionary Transition within the Circadian Clock
Kotwica‐Rolinska, J., Chodáková, L., Smýkal, V., Damulewicz, M., Provazník, J., Wu, B. C.-H., Hejníková, M., Chvalová, D., & Doležel, D. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab346 · Cited by 63 · see citing works
Expression of Timeless and Cryptochrome in Crustaceans
Bourgon, K., Connelly, J., Farthing, D., et al. (2014) · Digital Commons - Colby (Colby College)

Authors: Rubin, E. B., Shemesh, Y., Cohen, M., Elgavish, S., Robertson, H. M., & Bloch, G.
Affiliations: Hebrew University of Jerusalem (IL)
University of Illinois Urbana-Champaign (US)
ORCID: Shemesh, Yair
Elgavish, Sharona
Robertson, Hugh M.
Bloch, Guy
Venue: Genome Research
Publisher: Cold Spring Harbor Laboratory
Published: 2006-10-25
Volume: 16
Issue: 11
Pages: 1352-1365
ISSN: 1088-9051 (ISSN-L)
DOI: 10.1101/gr.5094806
PMC: PMC1626637
OpenAlex: W2114427883
Cited by: 257
References: 117
Citations by year: 2026: 6 · 2025: 8 · 2024: 15 · 2023: 15 · 2022: 12 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 13 · 2017: 22 · 2016: 12 · 2015: 9 · 2014: 15 · 2013: 7 · 2012: 19
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: Genome Research (publishedVersion, other-oa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Israel Science Foundation
National Institutes of Health
National Institute of Allergy and Infectious Diseases (AI56081, R01AI056081)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Insect and Arachnid Ecology and Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords: Apis mellifera, clock genes, cryptochrome, TIMELESS, period, cycles, insect circadian rhythms, foraging behavior
MeSH terms: Amino Acid Sequence, Animals, Bees, Brain, Circadian Rhythm, Drosophila, Molecular Sequence Data, Nuclear Proteins, Phylogeny, Species Specificity, Gene Expression, Genes, Insect, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Evolution, Molecular, Insect Proteins, Amino Acid Motifs, Drosophila Proteins, Mice, Period Circadian Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks