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New Vitamin D Research and the Evolution of Pigmentation

Pigmentation is a great model for teaching evolution and demonstrating the concept of a polygenic trait - there are a number of alleles at different loci at variable frequencies throughout the population.  This variability has been disproportionately seen across a latitudinal cline, with darker skin tones being present around equatorial regions, and a lightening seen as latitude increases. An estimated 88% of total pigmentation variation in humans can be explained by geographic differences; for reference, geography can only explain 13% of craniometric variation, another highly quantitative trait. Considering the recent evolution of modern humans, this drastic geographic distribution in pigmentation has been thought to be the result of strong selective pressures.

The major differences in pigmentation are due to the amount and type of melanin synthesized in the melanocytes, and the shape and distribution of the melanosomes, organelles that transport and store melanin . Melanins are classified as either Eumelanin (brownish/black) or Pheomelanin (reddish/yellow) - the difference is initially due to the presence of cysteine early on in melanin synthesis - a great example of how drastically different looking phenotypes don't have to have complex or 'magical' explanations *coughconservativechristianscough*. 

So what selective pressures led to the development of skin color? There are many hypotheses as to why we see this latitudinal gradient, most involving Uultraviolet Radiation (UVR). One major theory actually relates to nutrition - UV radiation, of which exposure is particularly high at the equator, can damage folate and its many metabolic intermediates - folates are essential for not only methylation events in the body but also nucleotide synthesis, spermatogenesis and prevention of neural tube defects - destruction of folic acid and its intermediates would've played a major selective pressure, ensuring the maintenance of dark pigmentation at these latitudes. However, as one moves away from the equator, there would be less nutrient lysis via UV degradation and therefore, less of a selective pressure exhibited by lighter skin colors. Interestingly, the data we have on MTHFR (a polymorphic enzyme in the folate pathway) is at higher frequencies in lighter skin toned populations, with U.S. whites and Japanese populations having as high as 35% prevalance, and remains quite low in darker skinned populations (<10%) (1) - why individuals in higher latitudes would have a higher prevalence of an enzyme with reduced activity is not entirely known. The other major selective factor used to explain the evolution of skin pigmentation is UVR's ability to damage skin. While skin cancer is generally something seen later in life and therefore, not a strong selective pressure, it has been noted that albino individuals in high UVR areas develop skin cancer in early adulthood, with less than 10% of them surviving beyond 30.

While these factors explain the maintenance of dark skin at the equatorial region, the evolution of lighter pigments at higher latitudes has been explained by selection for vitamin D synthesis, where vitamin D synthesis is thought to be reduced in dark skinned individuals at higher latitudes. I have been doubtful of this hypothesis for several reasons - while vitamin D is critical, to say that an insufficiency would be a strong enough selective pressure to see the drastic lightening in skin color is a big jump. Others (Robins) have cast doubt on this because Vitamin D synthesis in higher latitudes in the spring and summer months is probably adequate for storing/maintaining vitamin D levels. The counter argument to Robins has been "that vitamin D insufficiency is present in epidemic proportions at high latitudes, and that dark- skinned populations are at particular risk of vitamin D insufficiency". It is important to note that both light/white and dark/black skinned individuals at high latitudes are often considered vitamin D deficient, and that this difference is not due to different dietary intakes.

This is where a mix of older and newer research comes in.  Though dark skinned/black individuals have lower levels of serum vitamin D, they have consistently been found to have higher bone mineral density, and a lower risk of fragility fracture. Sounds counter-intuitive if they're deficient in Vitamin-D. A new study out in the New England Journal of Medicine (2) adds an interesting component to this evolutionary debate. In the study population, based on current recommendations, 77-96% of the black participants would be considered vitamin-D insufficient. However, these participants had higher bone mineral density/calcium levels than their white counterparts, of similar BMI and calcium intakes. The explanation provided by this research is the prevalence of a common variant of the Vitamin D binding protein gene. Current blood tests look for 25 hydroxycholecalciferol (25OH-D), and only a small portion of this is unbound and bioavailable. The blood test, which looks at total levels of 25OHD in the blood, takes into account bound and unbound forms. However, black individuals have lower levels of this binding protein, due to a higher prevalence (92.7%) of Gc1F variant of the Vitamin D binding protein; white individuals studied had a 6% prevalence of Gc1F. The authors conclude that just because the overall serum values of 25OHD appear lower in black individuals, this does not affect the amount of bioavailable 25OHD.

This study needs to replicated in a larger population of black individuals at different latitudes/in different seasons (and using antibodies that we're sure equally pull down different genotypes), but it could affect how we've interpreted the interactions between vitamin D and evolution of skin pigmentation. Theories have rested on selection for lighter skin colors to promote vitamin D synthesis. However, if the amount of bioavailable vitamin D is similar for dark and light pigmented individuals at higher latitudes, the evolution of pigmentation may be more related to other factors (potentially sexual selection).

The evolution of Vitamin D binding protein, also known as Gc-globulin, is an interesting issue to toss into the conversation. Gc-globulin binds vitamin D and its metabolites (cholecalciferol, calcidiol, calcitriol, 24-hydroxycholecalcidiol). Vitamin D3 that is incorporated into lipoproteins is the constituent of the plasma that is used by the liver for cholecalciferol hydroxylation to 25-hydroxycholecalciferol (25OH-D). The Gc-globulin bound vitamin D, mainly calcidiol, acts as a reservoir/storage site for the body (3).

Therefore, the prevalence of polymorphisms that lead to higher Gc-globulin bound Vitamin D in light skinned individuals may have been selected for, playing a role in ensuring stores of vitamin D at latitudes where synthesis may be compromised during non-spring/summer months. However, there seems to be less of a role for pigmentation in this model of vitamin D in evolution - light skinned individuals appear to have a higher prevalence of the Vitamin D binding protein alleles that confer higher storage levels, but how exactly pigmentation would've played a role in this needs to be explored. Other factors selecting for lighter skinned individuals could have occurred concomitantly with selection for this Vitamin D binding protein allele. The question remains: why couldn't dark skinned individuals have this allele that conferred higher vitamin D binding protein levels? Studying the total serum vitamin D levels in a  population of dark skinned individuals who, as a result of admixture, have copies of this allele may give some insight.


All evolutionary references come from: Esteban Parra. Human Pigmentation Variation: Evolution, Genetic Basis, and Implications for Public Health. 2007. Yearbook of Physical Anthropology. 50:85–105
1. http://www.nature.com/ki/journal/v65/n6/full/4494549a.html
2. http://www.nejm.org/doi/full/10.1056/NEJMoa1306357
3. David Bender. Nutritional Biochemistry of the Vitamins

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