Alpha-gal syndrome and the function of galactose-α-1,3-galactose in cows/pigs

My main question is: “What is the function and is it necessary for cows and pigs to have galactose-α-1,3-galactose?”

For context, this is involved in Alpha-gal syndrome, an allergic reaction to mammalian meat catalyzed by a tick bite. A person bitten by the specific tick develops this allergy to mammalian meat. However, I see research developing animals with a gene knockout that prevents the animal from producing galactose-α-1,3-galactose, presumably rendering them edible to those people with the allergic syndrome.

So…what is the purpose and function of galactose-α-1,3-galactose in these animals in the first place? Is it required for the health of the animal, or is it just one of those many carbohydrates that is just there and is not necessary for good health in the animal?

It’s more a question of why the line of primates we are part of suppressed it?

See discussion section page 1372. The guess is that some antibody against it had other protection against specific infectious diseases.

We still have other alpha galactose structures. Deficiency in breaking it down causes Fabry disease.

I’d guess it is involved in sphingolipids in other mammals but they retain more redundant pathways. Don’t know though.

To clarify my question. IF we are able to produce animals that lack galactose-α-1,3-galactose will those animals suffer any ill effects?

Since alpha-gal is a component of mammalian cell membranes (except for the parvorder that includes us), the question becomes “will the modified mammals have adequate cellular function with the engineered cell structure?”

The theory is that the loss of alpha-gal in certain primates was a random mutation that became advantageous for unknown reasons without being more deleterious that keeping the alpha-gal. Hard to beat natural selection, if you have enough time. I see a lot of trial and error for genetic engineers trying to replicate that and still have viable organisms.

Dang, primates are weird animals, apparently.

As I understand it, a popular explanation for why we lost the ability to produce vitamin C is because the reaction that does so produces a small amount of free radicals, which are harmful; so if we could get by with enough vitamin C from food, as our early primate ancestors who ate fruit could, then getting rid of this reaction was beneficial. I wonder if something similar happened here.

What’s odd is that the primate lifestyle doesn’t seem all that unusual. There are plenty of small arboreal animals that eat fruit. Why do primates have so many adaptations that we don’t see anywhere else?

Or maybe primates aren’t all that weird; maybe every animal group has some weird molecular quirks that we don’t necessarily know about, and we only pay attention when it happens to primates because we are primates.

My son does DNA research, and while most of what he talks about is way beyond me, one thing I do understand is that every gene, protein, amino acid, etc. has both primary and secondary effects and works both independently and synergystically with everything else. So your question is literally impossible to answer unless researchers can suppress the production of galactose-α-1,3-galactose and only that, then monitor for differences between the test group and control group.

In the interim, I’ve found the “Gal Safe” pigs have been approved by the FDA. I’m not seeing anything that indicates these modified pigs are suffering any ill effects. But I’ve just scanned the document.

To be very clear: the fact that a gene can be silenced with observable deleterious effect does not mean that the gene is “just there” or has no function. It may instead mean that there are redundancies; other genes, possibly originating from duplications, whose products also serve the same function. The advantage to having back ups for critical function genes is self-evident.

Again, the gene has been conserved among many species with our ancestral primate line being it seems the only path that silenced it. That puts humans at risk things like Fabry disease.

Silencing the gene was however selected for in our ancestral lineage. So at that point in history our ancestors gained some advantage to having it silenced that offset any disadvantage. Neither advantage or disadvantage had to be huge for that selection to occur.