Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging.
Mutations in the Caenorhabditis elegans gene clk-1 have a major effect on slowing development and increasing life span. The Saccharomyces cerevisiae homolog COQ7 encodes a mitochondrial protein involved in ubiquinone biosynthesis and, hence, is required for respiration and gluconeogenesis. In this study, RT-PCR and 5' RACE were used to isolate both human and mouse clk-1/COQ7 homologs. Human CLK-1 was mapped to Chr 16(p12-13.1) by Radiation Hybrid (RH) and fluorescence in situ hybridization (FISH) methods. The number and location of human CLK1 introns were determined, and the location of introns II and IV are the same as in C. elegans. Northern blot analysis showed that three different isoforms of CLK-1 mRNA are present in several tissues and that the isoforms differ in the amount of expression. The functional equivalence of human CLK-1 to the yeast COQ7 homolog was tested by introducing either a single or multicopy plasmid containing human CLK-1 cDNA into yeast coq7 deletion strains and assaying for growth on a nonfermentable carbon source. The human CLK-1 gene was able to functionally complement yeast coq7 deletion mutants. The protein similarities and the conservation of function of the CLK-1/clk-1/COQ7 gene products suggest a potential link between the production of ubiquinone and aging.
Vajo
Z
Z
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Dr. MSC 1852, Bldg. 10, Room 10C101, Bethesda, Maryland 20892-1852, USA.
King
L M
LM
Jonassen
T
T
Wilkin
D J
DJ
Ho
N
N
Munnich
A
A
Clarke
C F
CF
Francomano
C A
CA
D000375:Aging / Q000235:genetics*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005816:Genetic Complementation Test; D015801:Helminth Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014451:Ubiquinone / Q000096:biosynthesis* / Q000235:genetics; D015003:Yeasts
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D012333:RNA, Messenger; D014451:Ubiquinone; C030777:ubiquinone 7