Monday, November 15, 2010

Vitamin in Deeed!

According to many investigators and perhaps people seeking tidy hypotheses to explain evolutionary change, humans were black in the tropics where our species originated, to protect from the dangers of too much sun.  Even with dark skin, they got so many rays that they were able to make enough vitamin D. Vitamin D is obtained primarily by the effects of UV (solar) radiation enabling a vitamin-D producing reaction in the skin and only minimally by diet.

So we moved north, where there was less sunlight, and (as the story goes) were selected for lighter skin so we would not suffer disease due to vitamin D deficiency.  Such diseases supposedly include osteoporosis or other bone disease -- though if you believe the current hype, vitamin D deficiency (and how that's determined is another story; current thresholds would suggest that almost everyone is deficient) causes almost anything, from diabetes to cancer.  Whites get more UV light because, though there's less exposure in the high latitudes, they have less UV-filtering melanin in their skin.

So far so good.  But the lore on the relevant bone disease is 'fat, fair, female, and forty'.  Blacks as a group (in Europe and the US) do not have as much vit D deficiency-related problems, including  osteoporosis, as whites.  They do not get lots of rays in the north (or deep southern hemisphere) but they  don't need vit D supplements to reduce risk of fractures.

Now, a new study shows that whites who have vit D deficiency suffer strokes at a higher rate. Blacks are known to have higher rates of strokes in generally, but it's whites who apparently have higher stroke risk if they're vit D deficient.  This seems backward from the long-standing evolutionary story (or is it a Just-So story?), and it's not clear why. But what it does suggest is that lighter skin may not have evolved by natural selection in relation to vitamin D per se.

Strokes are serious, often crippling or fatal.  Usually, and probably much more so in pre-industrial times, strokes are rare or post-reproductive, so they have little impact on evolutionary fitness (natural selection).  Blacks in western environments have a higher risk of stroke, but this is generally thought to be due to the effects of lifestyle.  Many have argued that this (and the associated high blood pressure) is genetic--and all sorts of largely fanciful explanations have been offered for it (for example, that slaves whose bodies did not conserve salt died on the Middle Passage from Africa to the Americas).  But careful work by investigators including Charles Rotimi of NIH and Richard Cooper at Loyola Medical school in Chicago, both prominent and capable, have cast doubts on genetic explanations for this health difference.

Lighter skin has evolved at least twice (Europe and Asia) as people expanded north away from the tropics, and darker skin has evolved as Native Americans expanded from the arctic into the American tropics.  A recent and very good PhD student of our Department, Ellen Quillen, has shown in her dissertation some evidence for selection in at least a few genes related to pigment production.   There are always questions to be asked about this kind of research, and some important points have not yet been pinned down completely.  But at least it shows that evolutionary hypotheses related to skin color make considerable plausible sense.  But, then, what was the selective factor, if not health related to vitamin D?

We don't have the answer.  Except that ready acceptance of selective scenarios, rather than more careful and cautious approaches, is too often a part of evolutionary biology, and perhaps especially when it comes to humans.  We hunger to understand, but perhaps we also hunger too much to proffer hypotheses that are not fully baked.


occamseraser said...

Per your chairperson NJ, I thought skin pigments protected against UV-induced photolysis of folate (and thereby decreased the probability of neural tube defects)? If one rules out or minimizes the Vit D link, could loss of pigment outside of the tropics suggest "PMEs" rather than strong selection?

Holly Dunsworth said...

Hi Ken,
Forgive me but I'm not following this paragraph: "Now, a new study shows that whites who have vit D deficiency suffer strokes at a higher rate. Blacks are known to have higher rates of strokes in generally, but it's whites who apparently have higher stroke risk if they're vit D deficient. This seems backward from the long-standing evolutionary story (or is it a Just-So story?), and it's not clear why. But what it does suggest is that lighter skin may not have evolved by natural selection in relation to vitamin D per se."

How is it backwards and how does it weakened the vitamin D hypothesis?

Thanks much,

Ken Weiss said...

No hypothesis is too sacred to question. The neural tube defect issue was not part of the current story, and I don't know enough about the NTD connection with vitamin D. It's possible that the pigmentation evolution has some other origin, or that the current story about stroke is just something related to modern lifestyles.

If by PME you mean probable mutation effect, that is, that there's nothing to stop mutations interfering with pigmentation genes, that would not by itself seem plausible at least because there was repigmentation to some extent in the New World. There are at least some relevant genes, as we noted, that show some signatures of selection.

What we meant by 'backwards' is that more heavily pigmented people living in temperate climates would seem a priori to be more vulnerable to vitamin D deficient disorders. If there are other factors, like dietary sources or whatever, or if the current story is another bogus epidemiology report that won't be confirmed or is a reflection of confounding variables, then at least we should ask about those possibilities.

There are other possibilities that might be entertained. The tropics are more dangerous for infectious and parasitic disorders than colder climates as a rule, and pigmentation pathways are also relevant to immune function.

I would not claim to have the answers, but it is important (I think) to put every explanation, no matter how venerable, under the microscope.

Anne Buchanan said...

The idea here is that, as darker skinned people in northern latitudes have lower vitamin D levels than whites, but also lower rates of osteoporosis and now apparently of stroke (for a given vitamin D level) this suggests that the connection between vitamin D and skin color may perhaps be less straightforward than has been thought.

Though, I hasten to add that we haven't looked at the stroke study, and so can't say anything about the methods, but even if it isn't sound, the consistent inconsistency of the vitamin D/fracture story in African Americans compared with European Americans is pretty solid.

What does that mean? Who knows. Perhaps that bone mineralization happens in more than one way, depending on ancestral geographic origin? Which could indicate that risk of rickets in children is not completely dependent on vitamin D levels, depending on skin color?

The point is, as Ken says, that no hypothesis is sacred. A huge fraction of the cells in our bodies have vitamin D receptors so it's clearly important! But it does seem possible that we shouldn't assume that we all have equal vitamin D requirements for every function.

Ken Weiss said...

It's easy to overlook some of the complexities. Pigmentation around the world is generally constitutive (inherited in the usual genetic way). But not all vitamin D related traits are like this. Vit D receptor genotypes (at a particular marker site) and birth weight interact to affect bone mineral density in elderly people.

This may or may not relate to the post and comments. If the effect reported in the news is due to in utero environment it will have little if anything to do with evolutionary arguments, though it might affect any oversimplified attempt to use evolutionary scenarios in medical practice or public health.

Marcel F. Williams said...

Rickets can be the most fatal result of vitamin D deficiency since it can result in significant distortions in the pelvis of female children. And later, as an adult, such pelvic distortions could make delivering a child a lot more dangerous for both the child and the mother.

So the increased dangers of child birth would seem to be the most powerful selective agent for reducing pigmentation levels in high latitude populations.

Anne Buchanan said...

Yes, that's they hypothesis, and that's why it's especially interesting that people of African origin have less risk of fracture with lower levels of vitamin D than do light skinned people. There could be many explanations for this, but one possibility is that bone mineralization pathways aren't all the same. I certainly don't know that this is so, as this isn't my area, but I think the less than linear link between vitamin D levels and bone density makes the selective idea more complicated than usually suggested.

Ken Weiss said...

Earlier in a reply about PME I didn't perhaps clearly enough state that there might have been nothing _in northern climates_ that would prune out mutations that led to less pigmentation.

The darker skin of American tropical peoples is consistent with a re-evolution of pigmentation again in relation to UV light (though those populations, at least many of them, live in rainforest). But there are African populations without dark pigmentation, and dietary sources is part of the story, at least in relation to folate.

Skin pigmentation is affected by many genes, and they have different effects. The net selection effect in any given population may have been different, even for the same incoming UV amount, based on foods, culture, time of residence in an area, etc. Sexual selection may also have been important.

The paper we blogged on was a very over simplified one that did not deal with these issues, but should at least have recognized the curious aspects of the reported finding, if the finding is true rather than an artifact of the study.