Summary
Urate oxidase was lost in hominoids during primate evolution. The mechanism and biological reason for this loss remain unknown. In an attempt to address these questions, we analyzed the sequence of urate oxidase genes from four species of hominoids: human (Homo sapiens), chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), and gibbon (Hylobates). Two nonsense mutations at codon positions 33 and 187 and an aberrant splice site were found in the human gene. These three deleterious mutations were also identified in the chimpanzee. The nonsense mutation at codon 33 was observed in the orangutan urate oxidase gene. None of the three mutations was present in the gibbon; in contrast, a 13-bp deletion was identified that disrupted the gibbon urate oxidase reading frame. These results suggest that the loss of urate oxidase during the evolution of hominoids could be caused by two independent events after the divergence of the gibbon lineage; the nonsense mutation at codon position 33 resulted in the loss of urate oxidase activity in the human, chimpanzee, and orangutan, whereas the 13-bp deletion was responsible for the urate oxidase deficiency in the gibbon. Because the disruption of a functional gene by independent events in two different evolutionary lineages is unlikely to occur on a chance basis, our data favor the hypothesis that the loss of urate oxidase may have evolutionary advantages.
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References
Ames BN, Cathcart R, Schwiers E, Hochstein P (1981) Uric acid provides an antioxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 78:6858–6862
Antonarakis SE, Boehm CD, Giardina PJV, Kazazian HH Jr (1982) Nonrandom association of polymorphic restriction sites in the β globin gene cluster. Proc Natl Acad Sci USA 79: 137–141
Baserga SJ, Benz EJ Jr (1988) Nonsense mutations in the human beta globin gene affect mRNA metabolism. Proc Natl Acad Sci USA 85:2056–2060
Benton W, Davis R (1977) Screening lambda-gt recombinant clones by hybridization to single plagues in situ. Science 196: 180–182
Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol 18:225–239
Carothers AM, Urlaub G, Mucha J, Grumberger D, Chasin LA (1989) Point mutation analysis in a human gene: rapid preparation of total RNA, PCR amplification of cDNA, and Taq sequencing by a novel method. Biotechniques 7:496–499
Chiarelli B (1972) Taxonomic atlas of the living primates. Academic Press, London
Christen P, Peacock WC, Christen AE, Wackker WEC (1970) Urate oxidase in primate phylogenesis. Eur J Biochem 12: 3–5
Fanelli GM, Bohn DL, Russo HF (1970) Renal clearance of uric acid in nonhuman primates. Comp Biochem Physiol 33: 459–464
Fitch WM, Margoliash E (1967) Construction of phylogenetic trees. Science 155:279–284
Friedman TB, Polanco GE, Appold JC, Mayle JE (1985) On the loss of uricolytic activity during primate evolution-I. Silencing of urate oxidase in a hominoid ancestor. Comp Biochem Physiol 81B:653–659
Gibbs RA, Nguyen P-N, Caskey CT (1991) Direct DNA sequencing of complementary DNA amplified by the polymerase chain reaction. In: Mathew C (ed) Methods in molecular Biology. Humana (in press)
Goodman MB, Koop BF, Czelusniak J, Weiss ML, Slightom JL (1984) The η-globin gene: its long evolutionary history in the β-globin gene family of mammals. J Mol Biol 180:803–823
Keilin J (1959) Biological significance of uric acid on guanine excretion. Biol Rev 34:265–296
Lee CC, Wu X, Caskey CT (1989) Cloning the full-length cDNA for the porcine urate oxidase by the MOPAC generated probe. In: Mikanagi K, Nishioka K, Kelly WN (eds) Purine and pyrimidine metabolism in man VI. Plenum, New York, pp 499–505
Nakajima Y, Bourne GH (1970) Histochemical studies on urate oxidase in several mammals with special reference to uricolytic ability of primates. Histochemistry 22:20–24
Orowen E (1955) The origin of man. Nature 175:683–684
Proctor P (1970) Similar function of uric acid and ascorbate in man? Nature 228:868
Reddy PG, Nemali MR, Reddy MK, Reddy MN, Yuan PM, Yuen S, Laffler TG, Shiroza T, Kuramitsu HK, Usuda N, Chrisholm RL, Rao MS, Reddy JK (1988) Isolation and sequence determination of a cDNA clone for rat peroxisomal urate oxidase: liver specific expression in the rat. Proc Natl Acad Sci USA 85:9081–9085
Sanger R, Nicklen S, Coulson AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467
Shnitka TK (1966) Comparative ultrastructure of hepatic microbodies in some mammals and birds in relation to species differences in uricase activity. J Ultrastruct Res 16:598–625
Sibley CG, Ahlquist JE (1984) The phylogeny of the hominoid primates, as indicated by DNA-DNA hybridization. J Mol Evol 20:2–15
Urlaub G, Mitchell PJ, Ciudad CJ, Chasin LA (1989) Nonsense mutations in the dihydrofolate reductase gene affected RNA processing. Mol Cell Biol 9:2868–2880
Wu X, Lee CC, Muzny DM, Caskey CT (1989) Urate oxidase: primary structure and evolutionary implications. Proc Natl Acad Sci USA 86:9412–9416
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Wu, X., Muzny, D.M., Chi Lee, C. et al. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J Mol Evol 34, 78–84 (1992). https://doi.org/10.1007/BF00163854
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DOI: https://doi.org/10.1007/BF00163854