A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence
A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence
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DOI：
10.1073/pnas.95.20.11751
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发表时间：
1998-09-29
影响因子：
11.1
通讯作者：
Varki, A
中科院分区：
文献类型：
--
作者：
Chou, HH;Takematsu, H;Varki, A
唾液酸是后口动物重要的细胞表面分子。虽然人类不容易表达可检测数量的N-羟乙酰神经氨酸（Neu 5Gc，一种常见唾液酸N-乙酰神经氨酸Neu 5Ac的羟基化形式），但它是类人猿组织中的主要成分，除了大脑。这种差异与缺乏将CMP Neu 5Ac转化为CMP-Neu 5Gc的羟化酶活性相关。在这里，我们报告克隆人类和黑猩猩羟化酶cDNA。虽然这种黑猩猩的cDNA与鼠的同源物相似，但人的cDNA含有一个92 bp的缺失，导致移码突变。分离的人类基因也显示了这种缺失的证据。基因组PCR分析表明，这种缺失不发生在任何非洲大猿中，该基因在人类和大猿中均定位于6p 22-p23，这不对应于在类人猿进化期间发生的已知染色体重排。因此，导致现代人类的谱系在与黑猩猩和倭黑猩猩的共同祖先之后的某个时候发生了突变，可能影响各种内源性和外源性唾液酸结合凝集素的识别。此外，Neu 5Gc的表达以前报告在人类胎儿和肿瘤，以及在一些正常的成年人中检测到的痕迹，必须由一个替代途径介导。
Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts of N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form of the common sialic acid N-acetylneuraminic acid, Neu5Ac), it is a major component in great ape tissues, except in the brain. This difference correlates with lack of the hydroxylase activity that converts CMP Neu5Ac to CMP-Neu5Gc. Here we report cloning of human and chimpanzee hydroxylase cDNAs. Although this chimpanzee cDNA is similar to the murine homologue, the human cDNA contains a 92-bp deletion resulting in a frameshift mutation. The isolated human gene also shows evidence for this deletion. Genomic PCR analysis indicates that this deletion does not occur in any of the African great apes, The gene is localized to 6p22-p23 in both humans and great apes, which does not correspond to known chromosomal rearrangements that occurred during hominoid evolution. Thus, the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins. Also, the expression of Neu5Gc previously reported in human fetuses and tumors as well as the traces detected in some normal adult humans must be mediated by an alternate pathway.