Multiple changes in sialic acid biology during human evolution.
Multiple changes in sialic acid biology during human evolution.
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DOI：
10.1007/s10719-008-9183-z
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发表时间：
2009-04
影响因子：
3
通讯作者：
Varki A
中科院分区：
文献类型：
--
作者：
Varki A
人类在基因上与“类人猿”（黑猩猩、倭黑猩猩、大猩猩和红毛猩猩）非常相似，它们是我们进化过程中最亲近的亲戚。我们已经发现了人类和其他原始人在唾液酸和Siglecs（识别sia的Ig超家族凝集素）方面的多种遗传和生化差异。CMAH基因的失活突变消除了人类n -糖基神经氨酸（Neu5Gc）的表达，这是“类人猿”的主要唾液酸。另外还发现了人类特有的变化，影响了已知参与唾液酸生物学的60个基因中的至少10个。这对人类的独特特征以及人类对疾病的易感性或抵抗力都有潜在的影响。此外，来自动物源性材料的Neu5Gc代谢结合会发生在生物治疗分子和细胞制剂中，以及从饮食来源进入人体组织，特别是红肉和奶制品。由于人类也有不同的，有时是高水平的循环抗neu5gc抗体，这对生物技术产品和一些与慢性炎症相关的人类疾病有影响。
Humans are genetically very similar to “great apes”, (chimpanzees, bonobos, gorillas and orangutans), our closest evolutionary relatives. We have discovered multiple genetic and biochemical differences between humans and these other hominids, in relation to sialic acids and in Siglecs (Sia-recognizing Ig superfamily lectins). An inactivating mutation in the CMAH gene eliminated human expression of N-glycolylneuraminic acid (Neu5Gc) a major sialic acid in “great apes”. Additional human-specific changes have been found, affecting at least 10 of the <60 genes known to be involved in the biology of sialic acids. There are potential implications for unique features of humans, as well as for human susceptibility or resistance to disease. Additionally, metabolic incorporation of Neu5Gc from animal-derived materials occurs into biotherapeutic molecules and cellular preparations - and into human tissues from dietary sources, particularly red meat and milk products. As humans also have varying and sometime high levels of circulating anti-Neu5Gc antibodies, there are implications for biotechnology products, and for some human diseases associated with chronic inflammation.
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