Mutations Inactivating Biosynthesis of Dispensable Carbohydrate-Antigens Prevented Extinctions in Primate/Human Lineage Evolution.

IF 2.1 3区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Uri Galili
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引用次数: 0

Abstract

The human natural anti-carbohydrate antibodies anti-Gal, anti-Neu5Gc, and anti-Forssman are "living-fossils" that appeared in ancestral apes, monkeys and hominins millions of years ago. These antibodies appeared at various evolutionary periods in few mutated-offspring that lost the ability to synthesize the corresponding dispensable (i.e., nonessential) carbohydrate-antigens, α-gal epitope, Neu5Gc (N-glycolyl neuraminic acid) and Forssman-antigen, respectively. Production of these antibodies is stimulated by environmental antigens such as those of the human microbiota. Elimination of carbohydrate-antigens in the few mutated-offspring was caused by accidental nonsense or missense mutations that inactivated genes encoding enzymes involved in their biosynthesis, while most individuals in parental-populations continued synthesizing these carbohydrate-antigens. It has been suggested that dispensable carbohydrate-antigens which are absent in some mammalian species were evolutionary eliminated due to selective pressure by lethal viruses using these carbohydrate-antigens as "docking" receptors. An alternative selective mechanism which is based on the distribution of anti-Gal, anti-Neu5Gc and anti-Forssman in mammals, is presented in this review and is associated with the protective effects of these natural antibodies. It is suggested that epidemics of lethal enveloped-viruses caused the extinction of parental-populations synthesizing the corresponding carbohydrate-antigens of these antibodies,  independent of the cell adhesion mechanisms of such viruses. However, the few mutated offspring were protected by these natural antibodies which bound to carbohydrate-antigens synthesized on viruses as a result of their replication in individuals of the parental-populations. Recent studies suggest that these antibodies continue to contribute to the immune protection of humans against zoonotic infections by viruses presenting α-gal, Neu5Gc or Forssman antigens.

基因突变使碳水化合物抗原生物合成失活,阻止了灵长类/人类谱系进化中的灭绝。
人类天然抗碳水化合物抗体抗gal、抗neu5gc、抗forssman是数百万年前出现在猿、猴、人猿祖先身上的“活化石”。这些抗体在不同的进化时期出现在少数突变后代中,这些突变后代分别失去了合成相应的必要(即非必需)碳水化合物抗原、α-gal表位、Neu5Gc (n-乙醇基神经氨酸)和forssman抗原的能力。这些抗体的产生受到环境抗原的刺激,例如人类微生物群的抗原。在少数突变后代中,碳水化合物抗原的消除是由偶然的无义或错义突变引起的,这些突变使参与其生物合成的编码酶的基因失活,而亲本群体中的大多数个体继续合成这些碳水化合物抗原。有人认为,在一些哺乳动物物种中不存在的碳水化合物抗原,由于致命病毒使用这些碳水化合物抗原作为“对接”受体的选择压力,在进化中被淘汰了。本文提出了一种基于抗gal、抗neu5gc和抗forssman在哺乳动物体内分布的选择性机制,并与这些天然抗体的保护作用有关。这表明,致命包膜病毒的流行导致了亲本群体的灭绝,这些群体合成了这些抗体的相应碳水化合物抗原,而不依赖于这些病毒的细胞粘附机制。然而,少数突变的后代受到这些天然抗体的保护,这些抗体结合在病毒上的碳水化合物抗原上,这是它们在亲本群体个体中复制的结果。最近的研究表明,这些抗体继续有助于人类免疫保护,免受α-gal、Neu5Gc或Forssman抗原病毒的人畜共患感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Molecular Evolution
Journal of Molecular Evolution 生物-进化生物学
CiteScore
5.50
自引率
2.60%
发文量
36
审稿时长
3 months
期刊介绍: Journal of Molecular Evolution covers experimental, computational, and theoretical work aimed at deciphering features of molecular evolution and the processes bearing on these features, from the initial formation of macromolecular systems through their evolution at the molecular level, the co-evolution of their functions in cellular and organismal systems, and their influence on organismal adaptation, speciation, and ecology. Topics addressed include the evolution of informational macromolecules and their relation to more complex levels of biological organization, including populations and taxa, as well as the molecular basis for the evolution of ecological interactions of species and the use of molecular data to infer fundamental processes in evolutionary ecology. This coverage accommodates such subfields as new genome sequences, comparative structural and functional genomics, population genetics, the molecular evolution of development, the evolution of gene regulation and gene interaction networks, and in vitro evolution of DNA and RNA, molecular evolutionary ecology, and the development of methods and theory that enable molecular evolutionary inference, including but not limited to, phylogenetic methods.
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