Nishikimi M, Koshizaka T, Ozawa T, Yagi K
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Arch Biochem Biophys. 1988 Dec;267(2):842-6. doi: 10.1016/0003-9861(88)90093-8.
Humans, other primates, and guinea pigs are missing an enzyme L-gulono-gamma-lactone oxidase which catalyzes the last step of L-ascorbic acid biosynthesis. We have recently isolated a cDNA encoding this enzyme of the rat (T. Koshizaka, M. Nishikimi, T. Ozawa, and K. Yagi (1988) J. Biol. Chem. 263, 1619-1621). Northern blot hybridization using this cDNA as a probe demonstrated that guinea pigs lack mRNA for L-gulono-gamma-lactone oxidase. Nevertheless, existence of a DNA sequence related to this enzyme in the genome of this animal was shown by Southern blot hybridization. The human genome was also found to contain a sequence that is hybridizable with the cDNA probe; however, the degree of hybridization was less than those of hybridization with the L-gulono-gamma-lactone oxidase genes of animals possessing the enzyme, suggesting that the human L-gulono-gamma-lactone oxidase gene has diverged more rapidly than the genes of L-ascorbic acid-synthesizing species. This hypothesis was confirmed by comparison of a partial nucleotide sequence of the human gene with that of the rat one. The L-gulono-gamma-lactone oxidase-related sequences in the guinea pig and human genomes may represent the remnants of the gene of the enzyme that were once active but became nonfunctional during the course of evolution.
人类、其他灵长类动物和豚鼠缺乏一种催化L-抗坏血酸生物合成最后一步的酶——L-古洛糖酸-γ-内酯氧化酶。我们最近分离出了编码大鼠这种酶的cDNA（T. Koshizaka、M. Nishikimi、T. Ozawa和K. Yagi（1988年）《生物化学杂志》263卷，第1619 - 1621页）。用该cDNA作为探针进行Northern印迹杂交表明，豚鼠缺乏L-古洛糖酸-γ-内酯氧化酶的mRNA。然而，Southern印迹杂交显示该动物基因组中存在与这种酶相关的DNA序列。还发现人类基因组中含有一个可与cDNA探针杂交的序列；然而，杂交程度低于与拥有该酶的动物的L-古洛糖酸-γ-内酯氧化酶基因的杂交程度，这表明人类L-古洛糖酸-γ-内酯氧化酶基因的分化速度比L-抗坏血酸合成物种的基因更快。通过比较人类基因和大鼠基因的部分核苷酸序列，证实了这一假设。豚鼠和人类基因组中与L-古洛糖酸-γ-内酯氧化酶相关的序列可能代表了该酶基因的残余部分，这些残余部分曾经是有活性的，但在进化过程中变得无功能了。
