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Tuesday, June 22, 2010

Folate and not cancer caused dark skin and the ability to tan


It is well known that depigmentation in humans was caused because of the need of vitamin D generation at the skin, but what was not so clear was why pigmentation, dark skin (conventionally called black, though it's actually brown in most cases) first evolved.

Researchers from Pennsylvania State University have now concluded that skin cancer, which is a quite weak selective pressure, is not the main reason for dark skin but the protection of folate (folic acid, vitamin B9) from being destroyed by the ultraviolet radiation.

Much like vitamin D deficiency can cause major problems in newborns, folate deficiency also does, causing neural tube defects, anemia, low birth weight and premature births. Additionally, it also affects, although less severely, adults, causing weakness, depression, weight loss, headaches and behavioral disorders.

Nina G. Jablonski and George Chaplin, Human skin pigmentation as an adaptation to UV radiation. PNAS 2010. Freely accessible (it seems).

Also discussed at Science Daily.

20 comments:

Ken said...

5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA

"We demonstrate that 5-methyltetrahydrofolate (5-MTHF, the predominant folate in plasma) is also a potent, near diffusion limited, scavenger of singlet oxygen and quencher of excited photosensitizers. Both pathways result in decomposition of 5-MTHF, although ascorbate can protect against this loss. In the absence of photosensitizers, 5-MTHF is directly decomposed only very slowly by UVA or UVB. Although synthetic folic acid can promote DNA damage by UVA, submicromolar 5-MTHF inhibits photosensitization-induced strand breaks. These observations suggest a new role for reduced folate in protection from ultraviolet damage and have bearing on the hypothesis that folate photodegradation influenced the evolution of human skin color"

White skinned women have been intensively sunbathing for decades, where are the pregnancy problems or Folic acid deficiency among them?

"PUVA Treatment
PUVA treatment is the usage of UVA light in combination with psoralens (drugs) to make the skin hyper-photosensitive and is effective in the treatment psoriasis. However aside from any concerns about the UVA, the number of treatments must be carefully monitored and restricted over the lifetime of a patient due to the potential of liver damage caused by the psoralens".

This treatment using UVA and very powerful psoralens is what the study (Branda & Eaton1978) that Nina G Jablonski cites as evidence that folic acid is destoyed by sunlight was studying. This is does not square with the in vitro result of '5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA' which I have linked to. Here is confirmation of that in vivo Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial

"Our data suggest that both single and serial UVA exposures do not significantly influence serum folate levels in vivo."

Maju said...

Ok, fair enough. I know you are radically opposed to skin color being the most obviously adaptative trait in human diversification.

Guess I can delete your duplicate comment in the other, wrong, thread, right?

Ken said...

I am sure skin color is the most obviously adaptive trait in human diversification, I just don't think the melanized skin of black Africans or Bougainville Islanders evolved as an adaptation to prevent the destruction of folate. The living proof is the skin color of Khoisan Bushmen which is quite adequate for protection from the damaging effect of the sun exposure.

If someone could show there is a epidemic of "neural tube defects, anemia, low birth weight and premature births" among white women who live near the equator sunbathe or use sunbeds I might change my mind about Jablonski's folate hypothesis.


Don't get me wrong, apart fron the cancer risk whites probably are harmed by the level of sun exposure which is now common in activities such as sunbathing. Even in Britain the sun is too strong for the skin colour of Europeans and thats why their skins tan: for protective purposes.

Maju said...

Khoisanids live in a Mediterranean climate, just like North Africans or Italians. Give me a break.

All peoples in the tropical belt, excepting America (a recent arrival) share the dark pigmentation. All peoples outside it do not, and that includes Khoisanids.

"whites probably are harmed by the level of sun exposure which is now common in activities such as sunbathing".

Depends which 'whites'. Most are my skin shade and tan well. We are not as well protected from UV rays as 'blacks' but almost infinitely better than suboreal 'extreme whites'. Furthermore, we adapt very well to either extreme.

When tanned, people like me are rather like Khoisan, not like your usual Nordic "red crab".

It'd be interesting anyhow to figure what role plays pheomelanine, which is obviously not only present in red hairs but specially in black haired people like me and probably even in many black people, specially in Africa. But that's another story.

...

Anyhow, were you not the one who claimed that light pigmentation had nothing to do with vitamin D synthesis and that skin color was related to monogamy/poligamy (what is a total nonsense, because these cultural traits come and go and all hunter-gatherers are serially monogamous anyhow)

Ken said...

Tasmanian natives - there for over ten thousand years - were darker than any aboriginals to the north.

Whatever caused that it surely could not have been more intense UV radiation further south.

Maju said...

10,000 years is not much time (less than the arrival to tropical America). Australian Aboriginals are often quite dark and Australia is very desertic (i.e. open and sunny skies).

aargiedude said...

Ken, I'm partial to your point of view, but when you said this:

"White skinned women have been intensively sunbathing for decades"

I wonder if we would find that modern white people are receiving on average LESS sunlight then their ancestors a few generations ago. From farmland to city people. These scientists should compare white women who tan a lot with white women that don't, and see if there's a statistically significant effect on the babies.

I don't know what to think about this white/black skin evolution. It generally looks pretty clear, and the vitamin D theory looks great and I generally believe it, but then there are specific and not insignificant exceptions to this general rule:

1) The pygmies of Africa and New Guinea and the Amazon. Don't they live in the shades their whole life? Shouldn't they be whiter?

2) Again. These same people, personal impression, I may be wrong, seem to have a tendency to be darker than their grassland neighbors: Tasmanian forest people (only one I know for certain), perhaps the African pygmies, perhaps the Aborigines of Australia's small jungle region in the northeast.

3) Why aren't the grassland Indians of eastern Brazil as black as black Africans? Why aren't the Amazon Indians as black as the pygmies of the Congo Jungle?

The forest/grassland difference is the killer. Why would forest people be the same color as their grassland neighbors? The difference in sunlight falling on their bodies must be huge.

Maju said...

"Why aren't the grassland Indians of eastern Brazil as black as black Africans? Why aren't the Amazon Indians as black as the pygmies of the Congo Jungle?"

It's obvious: they have been living there only some 15,000 years at most and they migrated there through the Arctic, having lost the genetics of black pigmentation long before even stepping on Alaska. So they would need to re-evolve and that seems to need much more than just 10-15,000 years. Remember that humans and ancestors have been living in Tropical Africa for millions of years.

The jungle caveat is indeed more relevant and I have no satisfactory explanation other than:

1. Your judgment is subjective: the Dinka are for sure blacker than the Pygmies, the Tamils are generally darker than the Negritos.

2. Pygmies' territory used to be largely savanna for most of the Paleolithic.

And the like. Not conclusive, admittedly but at least something to chew on.

Ken said...

No Australian Aboriginals are as dark skinned as the Tasmanians were


Tasmanians must have have got darker in the 10,000 years since they separated from Australian Aboriginals, unless Austalian Aboriginals have got lighter in 10,000 years while the Tasmanians stayed dark for some reason.

Tasmania is at the same latitude in the South as Corsica is in the North!

Ken said...

vitamin D theory looks great

If white skin evolved to synthesisise extra vitamin D then
white people would have evolved to maximize vitamin D.

Well they don't!


A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations

"We speculate that recently identified U-shaped relationships between 25OHD concentrations and disease outcomes (i.e. increased risk at both high and low concentrations) may reflect a mixture of genotype-defined subgroups."


Genetics to Blame for Vitamin D Deficiency?


"Researchers conducted a genome-wide association study that involved almost 34,000 people of European descent from 15 different studies. They used radioimmunoassay and mass spectrometry to determine vitamin D concentrations and found that variants at three genetic sites, or "loci," were significantly associated with vitamin D concentrations. The presence of harmful alleles at three "loci" more than doubled the risk of Vitamin D insufficiency."

Maju said...

A black and white photo is hardly proof. Take for instance this W&B photo of aussies and tell me if you can discern any difference in the shades of grey...

The Australian Natives I have seen in so many documentaries range from milk chocolate brown to very dark brown (pure chocolate brown), with nothing to envy Africans, Papuans or whatever else in shade.

However the facial anthropometry of Trungannini, specially the eyes area, reminds a bit more of Papuans, while the usual Australian Native has more of a South Indian/Sinhalese vibe instead. But all within the common range of Australian natives.

...

Otherwise your links don't seem to say anything that changes the overall picture. If a handful of people have a genetic error affecting their vit. D metabolism, this is pretty much irrelevant. You're grabbing a burning nail, putting first your preconceptions in a pseudo-scientific endeavor. Wasting my time (again).

Ken said...

If a handful of people have a genetic error affecting their vit. D metabolism, this is pretty much irrelevant


No it's not just a handful

"At least two alleles reduce the effectiveness of the vitamin-D binding protein, and their homozygotes account for 9% and 18% of French Canadians (Sinotte et al., 2009)."

Which maybe explains why a study of highly sun exposed (tanned) heathy young skateboarders and surfers in Hawaii (where the sun is strong enough to make vitamin D all year)HERE found levels below the putative minimum of 30 ng/ml in 51% of the subjects.

Maju said...

Medicine is not an exact science, the human body is not a machine. That I learned from my physician relatives when a kid.

Maybe we are oversighting something, like a different vitamin D metabolism in adult males, for example. Remember that the most affected by all these issues are children and mothers, women are also more likely to have bone problems, specially after menopause. Finally 30 ng/ml is just the top risk level for osteoporosis and the top risk level for more severe illnesses is just 10 ng/ml.

Btw, the only person I know who did have osteomalacia was a young woman with rather dark skin for the average here (caramel without tanning), who had lived a lot in insides in her youth (for what I could gather).

aargiedude said...
This comment has been removed by the author.
aargiedude said...

Maju, I think evolving skin color is one of the quickest, simplest things regarding natural selection. It's just having more or less pigments per square cm of skin.

Disregard all the other observations I made, the fact that pygmies have skin as dark as their grassland neighbors (in Africa and evereywhere else) is THE problem with the vitamin D theory, which I still agree with, it's just that I'm very puzzled by this unexplainable phenomenon. All I can think of is that jungle hunter-gatherers, for whatever reason, really do manage to get a lot more Sun than we imagine, despite being in a deep forest.

Maju said...

I understand that the patterns of pigmentation are not so specific as to discern between jungle and non-jungle circumstances. Seemingly jungle dwellers manage well with dark pigmentation and hence do not need to depigment. Additionally the prehistorical circumstances may have been different, with more open areas in at least some cases (at least Africa) and also including interaction with neighboring inhabitants of more open areas (coasts, savanna, etc.), maybe now extinct in some cases.

If we consider only African variation, for instance (excluding North Africans, whose genetic background is essentially Eurasian), we see that only the group that has been most separated from the rest, Khoisans, in a subtropical environment, has evolved a clearly lighter pigmentation. So it seems to run across large populations rather than very specific ones.

Most diversity in this aspect is anyhow found among Eurasians, at least in phenotype, ranging from very dark to lightest, with at least two different evolutionary pathways to depigmentation: one in East Asia (extending to America) and another in West Eurasia.

These two different pathways, including all ecological factors, such as Europe being comparatively much warmer than all other regions at similar latitudes (except a small area of coastal NW America), and probably also random ones (such as founder effects), seem to explain well the patterns of pigmentation we see now. But this applies most perfectly at broad scales rather than if we go nit-picky, because even if there is a clear adaptative pressure, this one is seldom a life-or-death one but rather a mild one, whose effects can only be seen in the long run.

Maju said...

"By the way, I just noticed something about R1a and Iberia that is truly fascinating. I'm going to look at this more in depth tomorrow and then write about it. Here's a clue: your observation about that very rare mtdna lineage that has only been found in North Africa and Italy".

You mean JT(xJ,T), right?

You mentioned elsewhere about some apparent Ibero-African R1a sublineage. I'm intrigued but I don't yet grasp the matter clearly.

Ken said...

Re. ostiomalacia in a "young woman with rather dark skin for the average here (caramel without tanning), who had lived a lot in inside"

She wasn't a vegetarian by any chance?



aargiedude said...If we consider only African variation, for instance (excluding North Africans, whose genetic background is essentially Eurasian), we see that only the group that has been most separated from the rest, Khoisans, in a subtropical environment, has evolved a clearly lighter pigmentation.

Origins of black Africans
"It is often assumed that black Africans, out of all human populations, most closely resemble our common ancestral state. After all, is not Africa the cradle of humanity? And did not modern humans spread ‘out of Africa’ some 50,000 or so years ago?

Indeed, we are all offspring of Africa. What is less true is the assumption that evolution stood still there while continuing elsewhere. Yes, some African groups do approximate ancestral Homo sapiens in their mode of subsistence, family structure, and physical appearance. These are the Khoisan and pygmy peoples. They still live by hunting and gathering, are overwhelmingly monogamous, and have light-brown skin and gracile, almost childlike bodies."



effects can only be seen in the long run

But Europeans' skins only started changing from brown (not black, see above) about 15,000 years ago; what was natural selection doing for the previous 20,000 years


When European skin became white

Maju said...

"She wasn't a vegetarian by any chance?"

Not in the period where she had those bad habits, her teens. Actually not ever strictly speaking, though when I met her, in her 20s, she had began taking care of he health in a higienist way, what emphasizes diet but does not need to be veggie, much less strictly so.

Anyhow the problem was from an earlier period, where she just didn't go out enough.

"some African groups do approximate ancestral Homo sapiens in their mode of subsistence, family structure, and physical appearance. These are the Khoisan and pygmy peoples. They still live by hunting and gathering, are overwhelmingly monogamous, and have light-brown skin and gracile, almost childlike bodies".

Pygmies don't have light skin. Their bodies are not childlike, though they are small in size. Khoisan are not necessarily small: only Bushmen are (much taller than Pygmies in any case) but not Khoikhoi (Hottentots).

Anyhow, these are not the only people who have more or less continued the lifestyle of our common African ancestors but there are other groups like the Hadza.

Also when you look at fossils as Idaltu, the size of the skull suggests large body rather than small, so I'm not inclined to support the hypothesis that the early humans were small-bodied, at least not necessarily so. But those who lived in the tropical belt, as Idaltu himself, surely were pretty much black in pigmentation.

...

Regarding jungle lifestyle, I'm now chewing on the fact that our closest relatives truly adapted to jungle lifestyles (Pan sp.) have the following pigmentation pattern: young are white while adults are black. I'm not sure how to interpret this but it may be relevant because our biologies are not that different.

It also suggests that the different options re. pigmentation were there before the Pan-Homo split, whatever the exact role and pattern back then.

Maju said...

"But Europeans' skins only started changing from brown (not black, see above) about 15,000 years ago"...

That is just not true. There has been a lot of hype on certain gene and certain molecular clock estimates.

The reality is that this gene is just one of many involved in pigmentation and the chronology is anyhow probably wrong, as most molecular clock hunches are.

By how much, I can't say for sure but the fact that the allele is shared at similar overwhelming frequencies by CEU (essentially NW European by ancestry) and TSI (Tuscans), who have not interacted much since the Gravettian, suggests that the allele was there some 30,000 years ago.

Furthermore, GIH (Gujarati Indians from Houston) also share the same allele in almost as overwhelmingly manner, yet they are generally quite darker. So it's just an allele that was quite common before the colonization of West Eurasia, what gives it a time depth of at least 48,000 years, probably more.

The problem is that they find a gene that is different between CEU, CHB+JPT an YRI and they cry "whoa, pigmentation gene!", then they apply some more or less arbitrary equations and decide "whoa, 10,000 years ago!" But in the end reality is stubborn and proves them wrong.

I understand that the process of pigmentation modifications began already in South Asia, as there's a KITLG variant almost universal among Eurasians and then evolved and then continued with West and East branches but that much of it is still ill understood.

No Cro-Magnon (or similarly old) genome has been sequenced beyond mtDNA, we really know almost nothing about early modern human genetics directly. Just a little bit of mtDNA and we are more often than not unsure of its reliability.