Molecular Biology and Evolution 19:640-653 (2002)
© 2002 Society for Molecular Biology and Evolution
Loss of Urate Oxidase Activity in Hominoids and its Evolutionary Implications
*Department of Biosystems Science, Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa, Japan;
Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan
We have determined and compared the promoter, coding, and intronic sequences of the urate oxidase (Uox) gene of various primate species. Although we confirm the previous observation that the inactivation of the gene in the clade of the human and the great apes results from a single CGA to TGA nonsense mutation in exon 2, we find that the inactivation in the gibbon lineage results from an independent nonsense mutation at a different CGA codon in exon 2 or from either one-base deletion in exon 3 or one-base insertion in exon 5, contrary to the previous claim that the cause is a 13-bp deletion in exon 2. We also find that compared with other organisms, the primate functional Uox gene is exceptional in terms of usage of CGA codons which are prone to TGA nonsense mutations. Nevertheless, we demonstrate rather strong selective constraint against nonsynonymous sites of the functional Uox gene and argue that this observation is consistent with the fact that the Uox gene is unique in the genome and evolutionarily conserved not only among animals but also among eukaryotes. Another finding that there are a few substitutions in the cis-acting element or CAAT-box (or both) of primate functional Uox genes may explain the lowered transcriptional activity. We suggest that although the inactivation of the hominoid Uox gene was caused by independent nonsense or frameshift mutations, the gene has taken a two-step deterioration process, first in the promoter and second in the coding region during primate evolution. It is also argued that the high concentration of uric acid in the blood of humans and nonhuman primates has developed molecular coevolution with the xanthine oxidoreductase in purine metabolism. However, it remains to be answered whether loss of Uox activity in hominoids is related to protection from oxidative damage and the prolonged life span.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Tanaka, K. O. Koyanagi, and T. Itoh Highly Diversified Molecular Evolution of Downstream Transcription Start Sites in Rice and Arabidopsis Plant Physiology, March 1, 2009; 149(3): 1316 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnson, S. E. Perez-Pozo, Y. Y. Sautin, J. Manitius, L. G. Sanchez-Lozada, D. I. Feig, M. Shafiu, M. Segal, R. J. Glassock, M. Shimada, et al. Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes? Endocr. Rev., February 1, 2009; 30(1): 96 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Leow, C. Bueno, N. Trivedi, M. S. Parmar, J. Oh, H. Y. Won, S.-M. Kang, L. A. Hebert, B. Rovin, D. I. Feig, et al. Uric Acid and Cardiovascular Risk N. Engl. J. Med., January 29, 2009; 360(5): 538 - 541. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Schwarzschild, S. R. Schwid, K. Marek, A. Watts, A. E. Lang, D. Oakes, I. Shoulson, A. Ascherio, and and the Parkinson Study Group PRECEPT Investigator Serum Urate as a Predictor of Clinical and Radiographic Progression in Parkinson Disease Arch Neurol, June 1, 2008; 65(6): 716 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Y. Sautin, T. Nakagawa, S. Zharikov, and R. J. Johnson Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress Am J Physiol Cell Physiol, August 1, 2007; 293(2): C584 - C596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Safra, G. V. Ling, R. H. Schaible, and D. L. Bannasch Exclusion of Urate Oxidase as a Candidate Gene for Hyperuricosuria in the Dalmatian Dog Using an Interbreed Backcross J. Hered., November 1, 2005; 96(7): 750 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Choi, D. B. Mount, and A. M. Reginato Pathogenesis of Gout Ann Intern Med, October 4, 2005; 143(7): 499 - 516. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Vogt Urate oxidase (rasburicase) for treatment of severe tophaceous gout Nephrol. Dial. Transplant., February 1, 2005; 20(2): 431 - 433. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Johnson and B. A. Rideout Uric Acid and Diet -- Insights into the Epidemic of Cardiovascular Disease N. Engl. J. Med., March 11, 2004; 350(11): 1071 - 1073. [Full Text] [PDF]
|
|
|
|
 |
|
 W S Waring, S H Adwani, O Breukels, D J Webb, and S R J Maxwell Hyperuricaemia does not impair cardiovascular function in healthy adults Heart, February 1, 2004; 90(2): 155 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dahan, O. Devuyst, M. Smaers, D. Vertommen, G. Loute, J.-M. Poux, B. Viron, C. Jacquot, M.-F. Gagnadoux, D. Chauveau, et al. A Cluster of Mutations in the UMOD Gene Causes Familial Juvenile Hyperuricemic Nephropathy with Abnormal Expression of Uromodulin J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2883 - 2893. [Abstract] [Full Text] [PDF]
|
|