@article {331712,
	title = {Mutations Inactivating Biosynthesis of Dispensable Carbohydrate-Antigens Prevented Extinctions in Primate/Human Lineage Evolution},
	volume = {93},
	year = {2025},
	month = {2025/04/01},
	pages = {212 - 228},
	abstract = {<p>The human natural anti-carbohydrate antibodies anti-Gal, anti-Neu5Gc, and anti-Forssman are \&ldquo;living-fossils\&rdquo; 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\&nbsp;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 \&ldquo;docking\&rdquo; 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, \&nbsp;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.</p>
},
	isbn = {1432-1432},
	url = {https://doi.org/10.1007/s00239-025-10243-x},
	author = {Galili, Uri}
}
