I read in wikipedia that:

Galactose-alpha-1,3-galactose, commonly known as alpha gal, is a carbohydrate found in most mammalian cell membranes. It is not found in primates, including humans.

My question is : Why not?

In the sources for the wikipedia article about alpha gal allergy, I spotted the (pay-walled) article Evolution and pathophysiology of the human natural anti-α-galactosyl IgG (anti-Gal) antibody which has this to say in the abstract :

It is estimated that anti-Gal appeared in ancestral Old World primates less than 28 million years ago, possibly as a result of an evolutionary event which exerted a selective pressure for the suppression of α-galactosyl epitopes expression by inactivation of the gene for the enzyme α1,3 galactosyltransferase.

However this is more than a bit over my head, biology-wise.

  • $\begingroup$ That is because of the presence of IgE antibody. IgE response to alpha-gal causes anaphylaxis in humans. If you would like a more biological detailed mechanisms check out this article: ncbi.nlm.nih.gov/pmc/articles/PMC4600073 $\endgroup$ – m4rio Dec 12 '18 at 14:51
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    $\begingroup$ @m4rio Are you saying that having the IgE antibody causes us to not have alpha-gal ? If that's the case, that's just passing the buck : why do we have the IgE antibody in the first place ? $\endgroup$ – SCH Dec 12 '18 at 14:56

The general idea is that infectious agents use certain cell-surface proteins to enter the cell, and presumably recognize them by their particular glycoproteins. There are examples (cited in the extract below) of changes in e.g. blood group antigens in populations that are thought to convey (at least temporarily) an advantage against particular pathogens.

In this context, let me cite the rest of the section of the article that you didn’t have access to:

However, after the geographic separation of Africa and South America, Old World primates appear to have been subjected to a selective pressure for the suppression of autologous α-galactosyl epitope synthesis and for the subsequent production of anti-Gal. Possibly, an infectious agent endemic to the Old World, which was detrimental to primates, and which expressed α-galactosyl, or α-galactosyl like epitopes, exerted a selective pressure for the evolution of Old World primates able to suppress autologous α-galactosyl epitope expression. Thus, immune tolerance toward this epitope was lost and anti-Gal antibodies could be produced in these primates as a protective response to such putative pathogens.

An alternative scenario for the evolutionary suppression of α-galactosyl epitope expression could have been one in which ancestral Old World primates suppressed expression of these epitopes on their cell surface glycoconjugates as a result of exposure to a pathogen which exerted its detrimental effect via α-galactosyl epitopes functioning as receptors. A current example for such a pathogen is Clostridium difficile. Enterotoxin A produced by this pathogen was found to bind to the cells it damages through interaction with α-galactosyl epitopes on cell surface glycoconjugates [12, 56]. A bacterial toxin with a similar ligand specificity and which was detrimental to ancestral Old World primates could exert a selective pressure for the evolution of primates which suppressed the expression of α-galactosyl epitopes and, thus, lost the immune tolerance toward this carbohydrate structure.

[12] Clark GF, Krivan HC, Wilkins TD, Smith DF (1986) Toxin A from Clostridium difficile binds to rabbit erythrocyte glycolipids with terminal Galα-3Galβ1-4GlcNAc sequences. Arch Biochem Biophys 257:217 [56] Krivan HC, Clark GF, Smith DF, Wilkins DT (1986) Cell surface binding site for Clostridium difficile enterotoxin: evidence of a glycoconjugate containing the sequence Galα→3Galβ1→4GlcNAc. Infect Immun 53:573

Whatever the reason, the consequence of this was:

This also resulted in the loss of immune tolerance to the α-galactosyl epitope and the production of anti-Gal.

I presume this explains the IgE problem referred to in a comment, and I would consider this as an unfortunate side-effect of the change, and not a reason for it.


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