Over 125 million years ago, a new trait  showed up in some ancient mammals – a   trait that was invisible to the naked eye  and that seemed beneficial at the time.

This trait was a new chemical marker that appeared  on the surface of all of the animal’s cells,   a sugar molecule known as ‘alpha-gal’.

Alpha-gal is still found on mammal cells  today.

And, yes, in keeping with its   powerful, boss-sounding nickname,  it’s got a really important job.

It’s one of an array of molecules that  cells use to signal to the immune system   that they’re part of the body, so the  body doesn't start basically attacking itself.

And we know this molecule has been around  for a very long time, because it’s found   all over the mammal family tree, from  kangaroos, to aardvarks, to whales.

But there is one - and only one -  group of mammals that doesn’t have it:   the catarrhine primates, which are the  monkeys of Africa and Asia, the apes, and us.

Around 20 to 30 million years ago, our  ancestors stopped producing alpha-gal.

And not only have we lost it,   but we actively produce antibodies against  this molecule - which no other mammals do.

So what’s going on here?

Why did our  lineage ditch an otherwise-universal   feature of mammal biology and start  producing antibodies that target it?

Well, this unique trait of ours might  be the molecular legacy of an ancient   catastrophe: an outbreak of a  devastating, deadly pathogen.

We can tell that the catarrhine primates,  including us, lost alpha-gal sometime after   we split from our common ancestor  with the monkeys of the Americas   around 40 million years ago – because  those other primates still produce it.

And the ancient gene that makes  it is still in our genomes today,   lying dormant on our 9th chromosome,  having been inactivated by mutations.

So we have a pretty good understanding of  when and how we lost the ability to make   this molecule.

But why this happened  is a much more complicated question.

After all, it’s not like it left any  hard evidence in the fossil record.

And we’ve never seen it happen naturally  in any other mammal.

As far as we can tell,   in the entire evolutionary history of  mammals, it’s only happened to our group.

So, we’ve had to turn to evolutionary  theory and our understanding of the   immune system to try to tease out this story.

My first question is: what could turn  the loss of alpha-gal into an advantage?

Because, I mean, presumably this chemical was really  useful to a lot of other mammals for a long time.

So why would losing it end up  being helpful enough that our   ancestors ended up passing along the  inactivated gene to their descendants?

This has led to a fascinating,  but pretty dark, hypothesis.

We know that pathogens - especially really  deadly ones - have been a major driving   force in our evolution, thanks to the selective  pressure they put on the populations they infect.

And we know that our immune system is  constantly being shaped by the pathogens   it encounters - both over the course of an  individual’s life and over evolutionary time.

That’s kind of the whole point of it.

So here’s what might have happened: Around  20-30 million years ago, a deadly pathogen   that had alpha-gal on its surface might’ve  found its way into some ancient primates.

And since both the host and the pathogen  had the same molecule on their cells,   the immune systems of those primates  couldn't make antibodies against the   pathogen … without also targeting their own cells.

But, in this scenario, a small number of  individuals just happened to have mutations   that inactivated their alpha-gal gene, so  their cells didn’t have that molecule on them.

Now, random mutations happen all  the time – they create the natural   genetic variation that we see in every population.

Sometimes they’re harmful and are weeded  out of the gene pool by natural selection.

Sometimes they’re neutral.

And sometimes  they confer a survival advantage.

And this might’ve been one  of those advantageous times.

Because the mutants that didn’t  have alpha-gal could then make   antibodies that targeted the pathogen without  mistakenly locking onto their own cells, too.

This would’ve allowed their immune  systems to fight the pathogen,   which potentially helped them survive  and pass those genetic mutations along.

Another possible scenario is that the pathogen  used the host’s alpha-gal as a kind of   ‘docking’ site to attach to and infect  the host’s cells.

In this case, too,   primates losing that molecule  would have had better protection.

Either way, the pathogen was so deadly,  and the mutations so advantageous,   that the inactivated alpha-gal  gene became ‘fixed’ in our lineage… Meaning: the working version of  the gene disappeared entirely   from our gene pool as those that had it died out.

So, today, all catarrhine primates descend from  those mutant survivors of that horrible outbreak.

And we still carry their  inactivated alpha-gal genes,   as well as their ability to  produce antibodies against it.

In fact, antibodies that bind to alpha-gal are   among the most abundant types  of antibodies that we produce.

Which is one of the main reasons that we  can’t easily receive organ transplants   from other mammals.

Their cells and  tissues are covered in alpha-gal,   which our antibodies bind to  and our immune system rejects.

Now, while this whole story works in theory, it’s  really hard to conclusively prove or disprove.

Like so many things about the deep past, the  story of alpha-gal is a working hypothesis.

But!

We do have some observations that support it.

For one thing, we know that a lot  of pathogens have alpha-gal on them,   including some viruses,  bacteria, fungi, and protozoa.

So it’s totally possible that some  unusually dangerous version of one   of these emerged and plagued our ancestors.

And we know that, around 20 to 30  million years ago, the monkeys of   the Americas and the lemurs of Madagascar were  geographically isolated from the catarrhines.

This may explain why those other primates  still have alpha-gal on their cells.

Because, if the outbreak was  restricted to Eurasia and Africa,   then they wouldn’t have been exposed to  the pathogen – so they weren’t subjected   to the selective pressure that drove the  loss of that molecule in our lineage.

We can also look to modern experiments to try  to fill in the missing pieces of this puzzle.

For example, researchers deactivated  the alpha-gal gene in pigs in the lab,   and they found that those pigs almost immediately  started producing antibodies against the molecule.

This is a lot like what’s thought to have  happened in the ancestors of catarrhines   20 to 30 million years ago.

Those with the mutant, deactivated  version of the gene were innately   able to produce antibodies against alpha-gal.

And the advantage of that change  in protecting against pathogens?

We can test that in the lab, too.

Researchers have knocked out the alpha-gal  gene in lab mice.

Then they infected them   with pathogens that have that molecule, and then  measured how well the mice could resist them.

And those mice turned out to be better able  to resist infection by protozoa and bacteria.

But, they also found that this came at a cost.

Those mice stopped being able to reproduce  earlier in their lifespan than normal mice.

This seems like a classic evolutionary trade-off.

And it’s entirely possible that the loss of   alpha-gal led to the same trade-off in our  primate ancestors as it does to mice in the lab.

Those primates would have had better  protection against pathogens with alpha-gal.

But on the other hand, they  might’ve had fewer offspring.

Now, as for whether this still  affects us, we don’t actually know.

I mean, a lot of evolution has taken place between   now and then, so we might be compensating for our  shortened reproductive lifespans, if we do indeed have them in other ways.

And this tradeoff may partly explain why the total  loss of alpha-gal has been so rare in mammals.

It takes a really nasty pathogen, and  one that uses a particular molecule,   for such a loss to be beneficial.

That situation seems to have only  taken place in catarrhine primates,   leaving us with this odd biological  quirk 20 to 30 million years later.

Now, this is just a hypothesis,  though a plausible one,   and there are many aspects of why we lost  alpha-gal that we may never understand.

The details of this story, like  so many others in natural history,   might simply be lost to deep time.

But it only further proves that –  for literally billions of years – our   ancestors have had to contend with  all sorts of deadly pathogens.

And the evolutionary pressures they  put on us have shaped our genes,