So why are people Rh-? (part 2)

Part 1 is here.

Unfortunately, Googling “Why are people Rh-?” leads you down one of those fevered rabbit holes full of crazy. See, “Rh” was originally named after the rhesus monkey because some early blood work discoveries were done with monkey blood instead of human blood, probably for obvious reasons related to monkeys being more common lab subjects than humans. Rh+/Rh- blood in humans doesn’t actually have anything to do with rhesus monkeys. But some people have interpreted the Rh+/Rh- distinction as meaning that some people have monkey blood and are therefore descended from monkeys, while other people don’t have monkey blood and therefore aren’t descended from monkeys. They think Rh- folks are descended from reptiles or gods or angels or ancient human breeding experiments or something else.

I’ve got news for you. You’re all descended from apes. Yes, even you.

Can someone explain what, exactly, motivates these fever dreams of alien god blood? “Crazy” seems an inadequate answer, because most of these people can type in complete sentences and even form coherent paragraphs, in contrast to, say, schizophrenics, who as far as I know have difficulty with such tasks. Is it just a side effect of being too dumb to tell the difference between “things scientists believe are reasonably plausible” and “a guy claiming that Rh- people are space aliens with extra vertebrae?” Or maybe a critical percent of them are just 15?

Anyway, back on topic, since it seems basically like Rh- people shouldn’t exist, why do they? There are three basic possibilities:

  1. Random chance.
  2. Founder effect in some populations
  3. Some beneficial effect to being Rh- or heterozygous

If random chance were the solution, we’d expect to find Rh- people distributed in roughly equal quantities throughout the world, or much of it. This is not what we find. Rather, according to Wikipedia, Rh- is most common among the Basque people (21-36% of Basques are Rh-); fairly common among other Europeans (16%); rare among African Americans, who have some European admixture, (7%); occurs occasionally in Siberians (% not given); shows up in about 1% of Native Americans; and is almost totally unknown in Africans and “Asians.” (Remember that this only counts people who are homozygous for the negative allele; due to heterozygosity, approximately 10% of Native Americans have the the negative allele. By contrast, only 1% of “Asians” have the allele.)

If you’ve read a lot of my posts, that list should match a pattern you already know; you can see part of it at the top of the screen, but Haak’s data includes more of the relevant Siberian and Native American groups:

Click for full size
From Haak et al.

Click to get a good look. Unfortunately, different people use different colors on their charts, so “blue” or “yellow” don’t necessarily mean the same things on different charts. Luckily for us, the “dark blue” seems to represent the same thing in both charts.

Dark blue is an ancient, ancestral, shall we say indigenous DNA group that’s found in ancient European skeletons from places like Sweden and Hungary, and is found in large chunks in all modern European populations (Gypsies probably excepted.) Dark blue is also found, in smaller amounts, in some north African populations, west Asian (including the Caucasus and northern Middle East but not really the bulk of the Middle East,) India, and Siberia (the relevant groups here are the Chuvash, Mansi, Even, Selkup, Aleut, Tlingit, Yukagir, Tubalar, Altaian, Dolgan, and Yakut). It’s found in tiny bits in Native American DNA, either because Native Americans brought it with them when they crossed the Bering Strait, or because of recent European admixture. (Or both.)

Interestingly, the Basque have very little of the “teal” (light green in the graph at the top of the blog,) simply because teal was brought in with the Indo-European invasion and Basque aren’t Indo-European. Teal is also very common in India (Indo-European and all that,) but Rh- isn’t common in India.

The “orange” DNA (light blue at the top of the blog) is found throughout the Middle East, where Rh- isn’t, and isn’t found much in Siberia, where Rh- is.

In other words, the Dark Blue people left DNA in approximately the right amounts in all of the relevant people, and the other color-groups in the chart didn’t.

In Africa and Asia, it seems likely to me that the Rh- people actually are the result of random chance. But among the folks with Blue People admixture, I suspect that we are looking at a Founder Effect–that is, when the original band of hunter gatherers who became the Blue People split off from the other tribes, they just happened, by random chance, to have a higher than average percentage of people with Rh- alleles than the rest of the human population.

This happens all the time; if you were to just pick ten random people off the street and test their DNA, you’d likely find that your random population has some genes that are far more common or rarer than in humanity as a whole.

But this does not explain the persistence of Rh-, much less its rather high frequency among the Basque.

First, I want to stop and make a PSA about the Basque:

The Basque are not super people who descended directly from the gods, aliens, Neanderthals, the first primeval man, or whatever. They’re just some guys who, like the Sardinians, didn’t get conquered by the Indo-Europeans, and so never picked up an Indo-European language and held onto a slightly different culture, though they’ve had a ton of cultural contact with the Spanish and French over the years and probably all speak Spanish and/or French these days.

Humans–by which I mean “anatomically modern humans” as they are called–have been around for approximately 200,000 years. About 100,000-70,000 years ago, humans left Africa and spread out across the rest of the world. (We picked up our Neanderthal admixture around this time, so pretty much all non-Africans have Neanderthal DNA, and even the Africans probably have some Neanderthal DNA because it looks like some non-Africans later went back to Africa and intermarried with the people there, because humans have moved around a lot over the past 100,000 years.)

Indo-European, as a language family, didn’t get going until about 8,000 to 6,000 years ago. It didn’t reach France until about 3,000 years ago, and got to Spain even later.

In other words, the Basques are not the sole living descendents of the first peoples from 200,000 years ago, or Neanderthals from 40,000 years ago. They are among the few unconquered descendents of people who lived about 3,000 years ago. You know, about the time the Greeks and Romans were getting going, or maybe the Assyrian Empire. Not prehistory.

Back to our story.

Unfortunately, there isn’t a lot of research on why Rh- exists, but some folks have been pursuing the Toxoplasma Gondii angle. Basically, the idea is that if Sickle Cell Anemia exists because heterozygous sickle cell carriers are protected against malaria, even if folks who are homozygous for SSA die off.

Toxoplasma turns out to be one of the most common parasitic infections, infecting 30-50% of humans. I have yet to find what I consider a reliable-looking map of rates of T. gondii infection world-wide, but it infects about 22% of Americans over 12, and infection rates reach 95% in some places. (And 84% in France, probably due to bad hygiene and raw meat consumption.)

Even though T. gondii likes pretty much any warm-blooded host, they can only reproduce in cats/felids. So I wouldn’t expect any T. gondii in areas with no cats, like Australia before the Europeans got there.

One of the effects of T. gondii infection is slower reactions, so scientists have looked at whether people with Rh- blood or Rh+ blood have slower reactions with or without T. gondii infections.

The conclusions are kind of mixed, and I put this in the “needs more research” category due to some small Ns, but nevertheless, here’s what they found:

Among uninfected people in an ethnically homogenous population, Rh- males had faster reaction times than Rh+ males. However, when infected, the Rh-s become slower than the Rh+s (who showed very little change). But if we break the Rh+ group into homozygous Rh++ and heterozygous Rh+-s, we see something remarkable: the Rh++s have worse reaction times following infection, but the Rh+-s’ reactions times actually decreased!

The only problem with this theory is that T. gondii has probably historically been most closely associated with parts of the world with more cats, and Africa, the Middle East, and India historically had more cats than Europe, and certainly more than Siberia. If the idea is that being heterozygous is supposed to be protective against T. gondii, we’d expect to see more heterozygotes in areas with high rates of T. gondii, just as Sickle Cell Anemia is common in areas with malaria. We wouldn’t expect it in places like Siberia, where there are very few cats.

But perhaps the answer is more straightforward: Rh++ is protective against T. Gondii, but at the cost of lower reaction times. Rh– confers faster reaction times, but sucks against T. Gondii. Rh-s could therefore have an advantage over Rh++s and proliferate in areas with few cats, like Siberia.

But T gondii has had time to adapt to the older variant (Rh++;) Rh+- confuses it, thus offering protection against slower reaction times mostly by accident rather than positive selection for Rh+- people in areas with high levels of T. gondii.

Of course, this is all speculation; maybe folks in the Basque region have actually just had a lot of housecats and so contacted T. gondii more than other people, or maybe we’re just seeing an “Elderly Hispanic Woman Effect” due to the data being split into a lot of categories.

Things being as they are, I’d suggest studying the Basque and seeing if Basques with Rh- alleles have any traits that Basques with Rh+s don’t.

I really wish there were some more research on this subject! I guess we just don’t know yet.

ETA: I just realized something that, in retrospect, seems really obvious. If the French have an 85% T. Gondii infection rate, then the Basques–whose territory is partly in France and partly in Spain–may also have a very high infection rate. The French must have a ton of cats. Infection rates probably have more to do with the density of domesticated cats than of wild cats; the prevalence of Rh- and Rh+- alleles may have nothing to do with ancient cave people, but be a more recently selected adaptation. I don’t know when cats became common in Europe, but I’m guessing that plague-infested Medieval cities invited a fair number of cats. Hey, better T. Gondii than Yersina Pestis. If the Basques have somewhere near an 85% T. gondii infection rate, and have had it for a while–say, since the Middle Ages–their current high rates of Rh- blood may in fact be due to Rh+- folks being protected against the effects of infection.

I don’t know why I didn’t see that earlier.

Now I want to know whether people with T. Gondii are more likely to go on strike or start revolutions.

Why do Rh- People Exist?

Having the Rh- bloodtype makes reproduction difficult, because Rh- mothers paired with Rh+ fathers end up with a lot of miscarriages.*

The simplified version: Rh+ people have a specific antigen in their blood. Rh- people don’t have this antigen.

If a little bit of Rh+ blood gets into an Rh- person’s bloodstream, their immune system notices this new antibody they’ve never seen before and the immune response kicks into gear.

If a little bit of Rh- blood gets into an Rh+ person’s bloodstream, their immune system notices nothing because there’s nothing to notice.

During pregnancy, it is fairly normal for a small amount of the fetus’s blood to cross out of the placenta and get into the mother’s bloodstream. One of the effects of this is that years later, you can find little bits of their children’s DNA still hanging around in women’s bodies.

If the mother and father are both Rh- or Rh+, there’s no problem, and the mother’s body takes no note of the fetuses blood. Same for an Rh+ mother with an Rh- father. But when an Rh- mother and Rh+ father mate, the result is bloodtype incompatibility: the mother begins making antibodies that attack her own child’s blood.

The first fetus generally comes out fine, but a second Rh+ fetus is likely to miscarry. As a result, Female Rh- with Male Rh+ pairings tend not to have a lot of children. This seems really disadvantageous, so I’ve been trying to work out if Rh- bloodtype ought to disappear out over time.

Starting with a few simplifying assumptions and doing some quick back of the envelope calculations:

  1. We’re in an optimal environment where everyone has 10 children unless Rh incompatibility gets in the way.
  2. Blood type is inherited via a simple Mendelian model. People who are ++, +-, and -+ all have Rh+ blood. People with — are Rh-.
  3. We start with a population that is 25% ++, +-, -+, and –, respectively.

So our 1st generation pairings are:

F++/M++   F++/M+-   F++/M-+   F++/M–

F+-/M++    F+-/M+-    F+-/M-+    F+-/M–

F-+/M++    F-+/M+-    F-+/M-+    F-+/M–

F–/M++     F–/M+-      F–/M-+     F–/M–

Which gives us:

10++,           5++, 5+-       5+-, 5++     10+-

5++, 5-+      2.5++, 2.5+-, 2.5-+, 2.5–   2.5+-, 2.5++, 2.5–, 2.5 -+      5+-, 5–

5-+, 5++      2.5-+, 2.5–, 2.5++, 2.5+-    2.5–, 2.5-+, 2.5+-, 2.5++      5–, 5+-

1-+,         It’s complicated   It’s complicated   10–


50++,   40+-,   21-+,   30–,   and some quantity of “It’s complicated.”

For the F–/M+- pairings, any — children will live and most -+ children will die. Since we’re assuming 10 children, we’re going to calculate the odds for ten kids. Dead kids in bold; live kids plain.

Kid 1: 50% -+,                     50% —

Kid 2: 25% -+, 25% —       25% -+, 25% —

Kid 3: 25% -+, 25% —       12.5% -+, 12.5% —    12.5% -+, 12.5% —

Kid 4: 25% -+, 25% —       12.5% -+, 12.5% —     6.3% -+, 6.3% —      6.3% -+, 6.3% –

Kid 5: 25% -+, 25% —        12.5% -+, 12.5% —    6.3% -+, 6.3% —       3.1% -+, 3.3% —    3.1% -+, 3.1% —

Obvious pattern is obvious: F–/M+- pairings lose 25% of their second kids, 37.5% of their third kids, 43.3% of their fourth kids, 46.4% of their fifth kids, etc, on to about 50% of their 10th kids.

Which I believe works out to an average of 5–, 1+-

The outcomes for F–/M-+ pairings are the same, of course: 5–, 1+-

So this gives us a total of:

50++, 41+-, 22-+, 40–,  or  33% ++, 27% +-, 14% -+, 26% —  (or, 54% of the alleles are + and 46% are -).

(This assumes, of course, that people cannot increase their number of pregnancies.)

Running the numbers through again (I will spare you my arithmetic), we get:

35% ++, 32% +-, 11.8%-+, 21.4% —  (or, 57% of alleles are + and 43% are – ).

I’m going to be lazy and say that if this keeps up, it looks like the –s should become fewer and fewer over time.

But I’ve made a lot of simplifying assumptions to get here that might be affecting my outcome. For example, if people only have one kid, there’s no effect at all, because only second children on down get hit by the antibodies. Also, people can have additional pregnancies to make up for miscarriages. 20 pregnancies is obviously pushing the limits of what humans can actually get done, but let’s run with it.

So in the first generation, F–/M+- => 9–, 1+-  ; F–/M-+ => 9–, 1-+ (that is, the extra pregnancies result in 8 extra — children.) The F–/M++ pairing still results in only one -+ child.

This gives us 50++, 41+-, 22-+, 48– children, or 31%++, 25%+-, 13.7%, 30%– (or 51% + vs 49% – alleles.)

At this point, the effect is tiny. However, as I noted before, having 20 pregnancies is a bit of a stretch for most people; I suspect the effect would still be generally felt under normal conditions. For example, I know an older couple who suffered Rh incompatibility; they wanted 4 children, but after many miscarriages, only had 3.

Which leads to the question of why Rh-s exist at all, which we’ll discuss tomorrow.


*Lest I worry anyone, take heart: modern medicine has a method to prevent the miscarriage of Rh+ fetuses of Rh- mothers. Unfortunately, it requires an injection of human blood serum, which I obviously find icky.