Chou H H, Takematsu H, Diaz S, Iber J, Nickerson E, Wright K L, Muchmore E A, Nelson D L, Warren S T, Varki A
Glycobiology Program, Divisions of Hematology-Oncology and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11751-6. doi: 10.1073/pnas.95.20.11751.
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.
唾液酸是后口动物谱系中动物重要的细胞表面分子。虽然人类不易表达可检测量的N-羟乙酰神经氨酸（Neu5Gc，常见唾液酸N-乙酰神经氨酸Neu5Ac的羟基化形式），但它是除大脑外的大型猿类组织中的主要成分。这种差异与将CMP-Neu5Ac转化为CMP-Neu5Gc的羟化酶活性缺失有关。在此，我们报告了人类和黑猩猩羟化酶cDNA的克隆。虽然该黑猩猩cDNA与小鼠同源物相似，但人类cDNA包含一个92bp的缺失，导致移码突变。分离出的人类基因也显示出这种缺失的证据。基因组PCR分析表明，这种缺失在任何非洲大型猿类中均未发生。该基因在人类和大型猿类中均定位于6p22-p23，这与在类人猿进化过程中发生的已知染色体重排不对应。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间发生了突变，这可能会影响多种内源性和外源性唾液酸结合凝集素的识别。此外，先前在人类胎儿和肿瘤中报道的Neu5Gc的表达以及在一些正常成年人中检测到的痕迹必定是由另一条途径介导的。
