The capacity to biosynthesize ascorbic acid has been lost in a number of species including primates, guinea pigs, teleost fishes, bats, and birds. This inability results from mutations in the GLO gene coding for L-gulono-γ-lactone oxidase, the enzyme responsible for catalyzing the last step in the vitamin C biosynthetic pathway. We analyzed available primate and rodent GLO gene sequences to determine their evolutionary history. We used a method based on sequence comparisons of lineages with and without functional GLO genes to calculate inactivation dates of 61 and 14 MYA for the primate and guinea pig genes, respectively. These estimates are consistent with previous phylogeny-based estimates. An analysis of transposable element distribution in the primate and rodent GLO sequences did not reveal conclusive evidence that illegitimate recombination between repeats has contributed to the loss of exons in the primate and guinea pig genes.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Bánhegyi G, Csala M, Braun L, Garzó T, Mandl J (1996) Ascorbate synthesis-dependent glutathione consumption in mouse liver. FEBS Lett 381:39–41
Birney EC, Jenness R, Ayaz KM (1976) Inability of bats to synthesise L-ascorbic acid. Nature 260:626–628
Burns JJ (1957) Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid. Nature 180:553
Challem JJ (1997) Did the loss of endogenous ascorbate propel the evolution of anthropoidea and Homo sapiens? Med Hypotheses 48:387–392
Challem JJ, Taylor EW (1998) Retroviruses, ascorbate, and mutations, in the evolution of Homo sapiens. Free Radic Biol Med 25:130–132
Chatterjee IB (1973) Evolution and the biosynthesis of ascorbic acid. Science 182:1271–1272
Chaudhuri CR, Chatterjee IB (1969) L-ascorbic acid synthesis in birds: phylogenetic trend. Science 164:435–436
Chou H, Hayakawa T, Diaz S, Krings M, Indriati E, Leakey M, Paabo S, Satta Y, Takahata N, Varki A (2002) Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci USA 99:11736–11741
Coghlan A, Eichler EE, Oliver SG, Paterson AH, Stein L (2005) Chromosome evolution in eukaryotes: a multi-kingdom perspective. Trends Genet 21:673–682
Cooper DN (1999) Human gene evolution. BIOS Scientific, Oxford
Dabrowski K (1990) Gulonolactone oxidase is missing in teleost fish. The direct spectrophotometric assay. Biol Chem Hoppe Seyler 371:207–214
Dabrowski K (1994) Primitive actinopterygian fishes are capable of ascorbic acid synthesis. Experimentia 50:745–748
Drew KL, Osborne PG, Frerichs KU, Hu Y, Koren RE, Hallenbeck JM, Rice ME (1999) Ascorbate and glutathione regulation in hibernating ground squirrels. Brain Res 851:1–8
Drouin G, Prat F, Ell M, Clarke G (1999) Detecting and characterizing gene conversions between multigene family members. Mol Biol Evol 16:1369–1390
Echols N, Harrison P, Balasubramanian S, Luscombe NM, Bertone P, Zhang Z, Gerstein M (2002) Comprehensive analysis of amino acid and nucleotide composition in eukaryotic genomes, comparing genes and pseudogenes. Nucleic Acids Res 30:2515–2523
Graur D, Li W-H (2000) Fundamentals of molecular evolution, 2nd edn. Sinauer Associates, Inc., Sunderland, Massachusetts
Huchon D, Chevret P, Jordan U, Kilpatrick CW, Ranwez V, Jenkins PD, Brosius J, Schmitz J (2007) Multiple molecular evidences for a living mammalian fossil. Proc Natl Acad Sci USA 104:7495–7499
Hwang D, Lin T (2002) Effect of temperature on dietary vitamin C requirement and lipid in common carp. Comp Biochem Physiol B Biochem Mol Biol 131:1–7
Kolomietz E, Meyn MS, Pandita A, Squire JA (2002) The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors. Genes Chromosomes Cancer 35:97–112
Krasnov A, Reinisalo M, Pitkanen TI, Nishikimi M, Molsa H (1998) Expression of rat gene for L-gulono-gamma-lactone oxidase, the key enzyme of L-ascorbic acid biosynthesis, in guinea pig cells and in teleost fish rainbow trout (Oncorthynchus mykiss). Biochim Biophys Acta 1381:241–248
Li W, Maeda N, Beck MA (2006) Vitamin C deficiency increases the lung pathology of influenza virus-infected Gulo -/- mice. J Nutr 136:2611–2626
Linster CL, Van Schaftingen E (2007) Vitamin C biosynthesis, recycling and degradation in mammals. FEBS J 274:1–22
Moreau R, Dabrowski K (2000) Biosynthesis of ascorbic acid by extant actinopterigians. J Fish Biol 57:733–745
Murphy WJ, Pevzner PA, O’Brien SJ (2004) Mammalian phylogenomics comes of age. Trends Genet 20:631–639
Nakayama K, Ishida T (2006) Alu-mediated 100-kb deletion in the primate genome: the loss of the agouti signaling protein gene in the lesser apes. Genome Res 16:485–490
Nishikimi M, Kawai T, Yagi K (1992) Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species. J Biol Chem 267(30):21967–21972
Nishikimi M, Fukuyama R, Minoshiman I, Shimizux N, Yagis 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
Pace JK 2nd, Feschotte C (2007) The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage. Genome Res 17:422–432
Padh H (1990) Cellular functions of ascorbic acid. Biochem Cell Biol 68:1166–1173
Pascale E, Valle E, Furano A (1990) Amplification of an ancestral mammalian L1 family of long interspersed repeated DNA occurred just before the murine radiation. Proc Natl Acad Sci USA 87:9481–9485
Pauling L (1970) Evolution and the need for ascorbic acid. Proc Natl Acad Sci USA 67:1643–1648
Pollock JI, Mullin RJ (1987) Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of tarsius. Am J Phys Anthropol 73:65–70
Price AL, Eskin E, Pevzner PA (2004) Whole-genome analysis of Alu repeat elements reveals complex evolutionary history. Genome Res 14:2245–2252
Ray DA, Pagan HJT, Thompson ML, Stevens RD (2007) Bats with hATs: evidence for recent DNA transposon activity in genus Myotis. Mol Biol Evol 24:632–639
Rowold DJ, Herrera RJ (2000) Alu elements and the human genome. Genetica 108:57–72
Steiper ME, Young NM (2006) Primate molecular divergence dates. Mol Phylogenet Evol 41:384–394
Szabó Z, Levi-Minzi SA, Christiano AM, Struminger C, Stoneking M, Batzer MA, Boyd CD (1999) Sequential loss of two neighboring exons of the tropoelastin gene during primate evolution. J Mol Evol 49:664–671
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680
Toth G, Deak G, Barta E, Kiss GB (2006) PLOTREP: a web tool for defragmentation and visual analysis of dispersed genomic repeats. Nucleic Acids Res 34:W708–W713
Toyohara H, Nakata T, Touhata K, Hashimoto H, Kinoshita M, Sakaguchi M, Nishikimi M, Yagi K, Wakamatsu Y, Ozato K (1996) Transgenic expression of L-gulono-gamma-lactone oxidase in medaka (Oryzias latipes), a teleost fish that lacks this enzyme necessary for L-ascorbic acid biosynthesis. Biochem Biophys Res Commun 223:650–653
Uddin RK, Zhang Y, Siu VM, Fan Y, O’Reilly RL, Rao J, Singh SM (2006) Breakpoint associated with a novel 2.3 mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions. BMC Med Genet 7:18
Winter H, Langbein L, Krawczak M, Cooper DN, Jave-Suarez LF, Rogers MA, Praetzel S, Heidt PJ, Schweizer J (2001) Human type I hair keratin pseudogene phihHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence. Hum Genet 108:37–42
Zhang Z, Harrison PM, Liu Y, Gerstein M (2003) Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res 13:2541–2558
Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M (2010) Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates. Genome Biol 11:R26
Zilva SS (1936) Vitamin C requirements of the guinea-pig. Biochem J 30:1419–1429
We thank the two anonymous referees for their useful and constructive comments on a previous version of this manuscript. This work was supported by a Discovery Grant from the Natural Science and Engineering Research Council of Canada to G. D.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Lachapelle, M.Y., Drouin, G. Inactivation dates of the human and guinea pig vitamin C genes. Genetica 139, 199–207 (2011). https://doi.org/10.1007/s10709-010-9537-x
- Vitamin C
- L-gulono-γ-lactone oxidase
- GLO gene
- Unitary pseudogene
- Guinea pig