Jrk
Jrk | |||||||
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Identifiers | |||||||
Organism | |||||||
Symbol | Jrk | ||||||
Alt. symbols | bHLHe10, CG7391, clk, CLK, clock, CLOCK, dClck, dclk, dClk, dCLK, dCLK/JRK, dClock, dCLOCK, Dmel/CG7391, Jerk, jrk, Jrk, PAS 1 | ||||||
UniProt | O61735 | ||||||
Other data | |||||||
Chromosome | 3L: 7.76 - 7.78 Mb | ||||||
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dClock (clk) is a gene located on the 3L chromosome of Drosophila melanogaster. Mapping and cloning of the gene indicates that it is the Drosophila homolog of the mouse gene CLOCK (mClock). The Jrk mutation disrupts the transcription cycling of per and tim and manifests dominant effects.[1][2]
Discovery
Discovered at Brandeis University in 1998, cloning the mutant Jrk led to the identification of the drosophila homolog of the mammalian Clock gene in DNA.[2]
Jrk mutation
Jrk is a mutation of a gene (not to be confused with JRKL
Structure
Through complementation testing of Jrk with various deletions done by Allada et al., Jrk was found to be located on the left arm of chromosome 3, specifically at location 66A10-22.[2]
Start site: 7,763,233
Stop site: 7,775,603[6]
The dClock gene has a
The gene also has a
The gene has 5 transcripts, which encode for 4 unique polypeptides.[1][2] It has 9 exons.[9] The transcript of the gene is about 5000kB long, as determined through utilization of northern blot techniques.[1] The polypeptide that the transcript encodes for has a reported size between 1015 and 1027 amino acids, and a molecular weight between 130 and 150kD.[1][2]
Function
Circadian clock
In Drosophila, there are two main players in the generation of circadian rhythms: the period (per) gene and timeless (tim). These two genes are responsible for the oscillations in protein levels, RNA levels, and transcription rates that occur in flies.[1][2]
Another essential component of this circadian clock mechanism is that the PER protein contains a PAS domain, which has been demonstrated to mediate the interactions between transcription factors. These transcription factors also contain the well-characterized basic helix-loop-helix (
Jrk mutant phenotypes
The mutant Jrk allele is a consequence of a point mutation, which is simply the insertion, deletion, or swapping of one nucleotide base in an mRNA sequence for another. This mutation exhibits a dominant negative effect, meaning that just one copy of it is enough to produce phenotypic deviation. The Jrk mutation deletes much of the gene that encodes for the glutamine (Q)-rich C terminus of the protein. This region is involved in transcriptional activation, which is necessary to allow mRNA to be transcribed from DNA in the nucleus.[2] It can be achieved by utilizing ethyl methanesulfonate (EMS) as a mutagen.[1] The mutation results in a cytosine being swapped for a thymine at the 7764959 position (C7764959T).[10] This substitution causes what was initially encoded as a glutamine to be swapped for a premature stop codon, preventing further translation of the gene.[11]
Jrk was identified as a homozygous mutant with completely arrhythmic locomotor behavior in constant darkness. Approximately half of all of the Jrk heterozygotes were arrhythmic, and those that did manifest a rhythm had a slightly longer period than the wild-type controls.[1][2]
Researchers also observed that both PER and TIM levels are extremely low and non-cycling in homozygous Jrk flies, approximately equivalent to the trough levels of wild-type flies. In heterozygotes, PER and TIM cycle well, but the amplitude is reduced by approximately 50%, consistent with the clear effects on behavioral rhythmicity in these flies.[1][11]
Mammalian homologs of dClock
The Jrk gene has a myriad of
Mammalian mutations in the Clock gene have been found to result in autism spectrum disorder, schizophrenia, attention‐deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder.[13]
See also
- Clock gene
- Period (gene)
- Cycle (gene)
- Timeless (gene)
- Chronobiology
- Oscillating gene
- Michael Rosbash
- TTFL
References
- ^ a b c d e f g h i j k Limar ER. "Paper Alert". Current Opinion in Neurobiology. 8 (4): 437.
- ^ PMID 9988221.
- ^ "JRKL - Jerky protein homolog-like - Homo sapiens (Human) - JRKL gene & protein". www.uniprot.org. Retrieved 2019-04-11.
- S2CID 41757017.
- PMID 29172879.
- ^ a b "Gene: Clk (FBgn0023076) - Summary - Drosophila melanogaster - Ensembl genome browser 96". useast.ensembl.org. Retrieved 2019-04-11.
- ^ "PAC motif (IPR001610) < InterPro < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-04-11.
- PMID 15186484.
- ^ "Clk Clock [Drosophila melanogaster (fruit fly)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-04-11.
- ^ "FlyBase Allele Report: Dmel\Clk[Jrk]". flybase.org. Retrieved 2019-04-11.
- ^ PMID 9630223.
- PMID 33862929.
- PMID 28902457.
External links
- "Gene Report: Dmel\Clk". FlyBase. flybase.org.