APOL1 Variants

Apolipoprotein LI is a serum protein, a component of HDL, sometimes called ‘good cholesterol’.  It has another function: it protects people from trypanosomal infections – the kind of protozoa that cause sleeping sickness.  That is, it protects against most of them.  Two strains can get past this defense: T.b. gambiense and T.b. rhodesiense.

The APOL1 defense is a nonstandard innate immune  defense, specific for trypanosomes.  It chops holes in their surface membranes.  You need this in sub-Saharan Africa, because  the adaptive immune system can’t deal with trypanosomes, due to their vast repertoire of  coat antigens.

So when  you’re bitten by a tsetse fly carrying one of the two strains that have developed resistance to APOL1, you die, without modern (and fairly unpleasant) medical treatment.  Unless you’re a mutant.

This used to be a major problem, although the risk is lower nowadays.  Here’s a map of the areas subject to sleeping sickness:


Note that cattle (and horses) don’t have APOL1.

It turns out quite a few people who live in or whose ancestors originated in Sub-Saharan Africa have mutated versions of APOL1, changed in ways that  protect against one of the  dangerous strains.  These mutations don’t look all that old, probably less than ten thousand years. I would guess that humans made up an insignificant fraction of potential trypanosomal targets before the development of agriculture, so that there essentially no selection for versions that could get past human defenses.  After our numbers increased, strains that could infect humans were favored, and sometime after that,  mutations that protected humans against those dangerous strains began to spread.

The problem is that people with two copies of these protective variants are much more likely to experience kidney failure in later life.  African Americans are 4-5 five times more likely to end up on dialysis than whites.   It used to be that the medicos thought that the kidney risk was caused by increased levels of hypertension – now it looks as if it’s probably the other way around.

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26 Responses to APOL1 Variants

  1. Greying Wanderer says:

    I love maps like that.

  2. Wanderer says:

    Nothing in biology (or medecine) makes sense except in the light of evolution.

  3. dearieme says:

    Chuck it, Cochran: race is a social construct. Clearly 80% of African-Americans are just faking kidney illness and should be thrown out of the hospital. No doubt the Forces of Progress agree with me.

  4. dave chamberlin says:

    “you can’t go home again: Neanderthals”

    I would like to see a world map showing the Neanderthal percentage in modern populations. Funny how I’ve never seen one, I wonder why.

  5. MikeP says:

    Hmm, I wonder if anything similar has evolved among Central and South American Indians in response to Chagas’ disease.

    • gcochran9 says:

      I don’t think that Chagas hits as many people, so the selective pressures may not be as strong. It would seem that the APOL1 defense does not work against Chagas.

      • TWS says:

        My brother caught malaria and dengue fever in Central America. He recently died of heart failure. Reading the entry on Chagas disease, it looks like he could have had that as well. He had all the symptoms.

      • Anonymous says:

        In the Central American strain it commonly affects the nerves leading to the heart. I believe they use pacemakers to address the problem. In the South American strain it tends to affect the nerves leading to the colon. Even though the vector is an assasin bug, infection rates are not insignificant in rural areas of both Central and South America.

  6. Steve Sailer says:

    On average, East Africa is a better place than West Africa, due to altitude. Expats in Africa have the acronym WAWA: “West Africa wins again.” In this disease map, you can see the north-south stretch of East Africa that Cyril Rhodes had his eye on.

    By the way, there’s an island in Lake Victoria that doesn’t have tsetse flies and doesn’t have large mammals that compete with humans. The culture on the island seems more like, say, Burma than most of Africa: high density population up against Malthusian limits, with hard-working farmers who use clever techniques to maximize output. A lot of people leave the island due to overpopulation, but their descendants quickly take on the more lackadaisical work attitudes of the underpopulated and disease-infested mainland.

    I’ve always wondered what the small highlands of Cameroon are like.

    • athEIst says:

      nit-picker Cecil not Cyril.

    • dave chamberlin says:

      Someday history will get it right. Someday history will emphasize how some societies go through the misery of people pushed right to the Malthusian limit combined at the same time with increased survival rate of those with higher intelligence. Continue this for enough centuries and a population can become transformed in what it can accomplish.

      But it seems I’ll have a long time to wait because at present there aren’t enough foolish upstarts (he’s a racist! shut him up!) challenging the notion that maybe evolution works on us too. Until then I’ll be reading history about empires and kings always exaggerating the rock-em sock-em action that sells books and keeps couch potatoes fingers off the channel changer.

      History isn’t about the poor sad struggler who worked a little smarter and worked a little harder than his siblings and because of that he’s our ancestor while his bothers and sisters are not. But it should be because it is an important truth about what we now are.

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  8. bbartlog says:

    Looks like genetically engineering cattle to express APOL1 would be an interesting thing to try. Not that it would be good for the native fauna of Africa in the long run…

  9. teageegeepea says:

    I recall Greg arguing schizophrenia was probably the result of a pathogen (with the incidence by month of birth being a big indicator). Here’s an extended argument that the culprit is a retrovirus whose activation is triggered by other infections.

    • teageegeepea says:

      I saw it on Razib’s sidebar today and only just noticed the article is three years old.

    • gcochran says:

      Right how it looks as if mutation accounts for most schiz, but pathogens may be involved as well. The more the better: they’re a lot easier to deal with than genetic flaws.

      • erica says:

        If mutations account for most schiz cases, then why the season of birth effect? Or do you mean mutation + a pathogen trigger (which is more likely to occur during winter/spring) likely combine to account for most cases?

    • dave chamberlin says:

      From what I have read schizophrenia works much like the APOL1 mutation. One gene good, two genes bad, and that is why schizophrenia is still around. As with all genes effecting brain function it is more complex than that but the principle still holds. Get the wrong mix of genes and you are inclined towards schizophrenia, get the right mix and you are inclined to higher intelligence. I’m sure Cochran can explain this better than I can as it is part of his overclocking theory that evolution has pushed humans too hard and too fast regarding IQ with deleterious side effects.

  10. Sam says:

    Does temperature influence cognition via the practicality of heat being generated by the brain? Either evolutionarily or on a day to day basis?

  11. Jim says:

    I thought the schizophrenia concordance for identical twins is only about 50%. So it seems that although genetics produces a high risk there are also non-genetic factors.

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