Locus GULOP in the human genome is the site of a pseudogene called GULOP. In most mammals this is an active gene encoding the enzyme L-glucono-γ-lactone oxidase. This is the enzyme that catalyzes the last step in the synthesis of ascorbic acid (vitamin C). The gene is defective in humans and other primates so we can't make ascorbic acid and that causes scurvy if we don't get enough ascorbic acid in our food (Scurvy and Vitamin C).
The GenBank entry for this pseudogene is GeneID=2989. GULOP is located on chromosome 8 at p21.1 in a region that is rich in genes (map).
The human pseudogene was first identified by Nishikimi and Yagi (1991) using the intact rat gene (GeneID=60671) as a probe. They cloned and sequenced four exons that contained several deletions and several in-frame stop codons. This allowed them to conclude that the human pseudogene could not make a functional product. Several of these same mutations are found in chimpanzees, orangutans and macaques indicating that the inactive GULOP gene in all primates descends from a common ancestor that also had an inactive gene (Ohta and Nishkimi 1999).
Subsequent analysis on the GULOP locus in the human genome reveals that the pseudogene is missing most of the 5' exons that are present in the intact rat gene. In particular, exons I to VI are completely absent in the human genome. It is not known whether this deletion is responsible for the original inactivation of the GULOP gene in the primitive ancestral primate (Nishikimi et al. 1994; Ohta and Nishikimi 2003).
The human locus is also missing exon XI. In this case the deletion is probably due to recombination between Alu sequences that flank the site of the deletion. This deletion probably took place after the original inactivation event.
Inai, Y., Ohta. Y., and Nishikimi, M. (2003) The whole structure of the human nonfunctional L-gulono-gamma-lactone oxidase gene--the gene responsible for scurvy--and the evolution of repetitive sequences thereon. J Nutr Sci Vitaminol (Tokyo) 49:315-319.
Nishikimi, M. and Yagi, K. (1991) Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis. Am. J. Clin. Nutr. 54(6 Suppl):1203S-1208S.
Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. and Yagi. K. (1994) Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269:13685-13688.
Ohta, Y. and Nishikimi, M. (1999) Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis. Biochim. Biophys. Acta. 1472:408-411.