Brain growth genes
Back in 2005, it was found that human populations vary considerably at two genes, ASPM and microcephalin, that control the growth of brain tissue. The finding seemed to be ‘huge’ in its implications. Then, it all fizzled out. No correlation could be found between variation at either gene and differences in mental ability or head circumference (Mekel-Bobrov et al., 2007; Rushton et al., 2007).
A recent study has now shown that ASPM and several other genes (MCPH1, CDK5RAP2, CENPJ) do in fact influence growth of brain tissue, specifically cortical tissue. Moreover, this influence seems to be strongest for the regulatory regions of these genes, i.e., the portions that regulate the behavior of other genes. But why did earlier studies fail to find anything? One reason is that the software at the time was not sophisticated enough to calculate cortical surface area (as opposed to overall brain volume). Another reason is that earlier studies focused on the non-regulatory regions of these genes.
In 2010, we’ll probably see further developments in this area. Stay tuned …
Early modern human genome
Scientists have retrieved mtDNA from a 30,000 year-old hunter-gatherer from Kostenki, Russia. This seems to be part of a trend to study the genome of early modern humans. The challenge now will be to reconstruct not only the mtDNA but also the nuclear DNA—a serious problem because contamination from contemporary human sources cannot easily be ruled out. Significantly, Prof. Paabo has discovered several ways to minimize contamination.
Population differences in vitamin D metabolism
This year will see further evidence that natural selection has caused differences in metabolism among different human populations, including vitamin D metabolism.
For instance, many populations have long been established at latitudes where vitamin-D synthesis is impossible for most of the year. Some of these populations can get vitamin D from dietary sources (e.g., fatty fish) but most cannot. In these circumstances, natural selection seems to have adjusted their metabolism to reduce their vitamin-D requirements. We know that the Inuit have compensated for lower production of vitamin D by converting more of this vitamin to its most active form (Rejnmark et al., 2004). They also seem to absorb calcium more efficiently, perhaps because of a different vitamin-D receptor genotype (Sellers et al., 2003). Even outside the Arctic zone, there seem to be differences in vitamin-D metabolism from one population to another. In particular, vitamin-D levels seem to be generally lower in darker-skinned populations (Frost, 2009).
These findings will force us to revisit the vitamin-D hypothesis of European skin color. According to this hypothesis, Europeans are white-skinned because their ancestors had to maintain the same level of vitamin-D synthesis at latitudes where UVB radiation is much weaker. This leaves unexplained the much darker skin of indigenous peoples at similar latitudes in northern Asia and North America. More importantly, it posits vitamin-D metabolism as a ‘given’ that human skin color has to adjust to, when in fact this metabolic pathway is just as amenable to natural selection as everything else.
There probably is a causal link between white skin and European vitamin-D metabolism, but the sequence of cause and effect may run in the opposite direction:
1. European skin whitened for an unrelated reason, probably sexual selection.
2. Because this depigmentation ensured abundant vitamin-D synthesis in the skin, there was a relaxation of selection pressure on vitamin-D metabolism. This would explain why, in comparison to other populations, Europeans convert less of it to its most active form and why it binds less effectively to the type of vitamin-D receptor that is most common among Europeans.
Unfortunately, our norms for adequate vitamin intake are based on subjects or populations of European origin. We are thus diagnosing vitamin-D deficiency in non-European individuals who are, in fact, perfectly normal. This is particularly true for African Americans, nearly half of whom are classified as vitamin-D deficient, even though few show signs of calcium deficiency—which would be a logical outcome. Indeed, this population has less osteoporosis, fewer fractures, and a higher bone mineral density than do Euro-Americans, who generally produce and ingest more vitamin D (Frost, 2009).
By pathologizing non-Europeans as being vitamin-D deficient, modern medicine is paving the way for programs that are well intentioned but ultimately tragic in their consequences: mass vitamin-D supplementation to be dispensed through the school system and awareness campaigns. Such public health programs have already been proposed for African Americans and northern indigenous peoples.
What will be the outcome of raising vitamin-D levels in these populations? Keep in mind that we are really talking about a hormone, not a vitamin. This hormone interacts with the chromosomes and gradually shortens their telomeres if concentrations are either too low or too high. Tuohimaa (2009) argues that optimal levels may lie in the range of 40-60 nmol/L. In non-European populations the range is probably lower. It may also be narrower in those of tropical origin, since their bodies have not adapted to the wide seasonal variation of non-tropical humans.
If this optimal range is continually exceeded, the long-term effects may look like those of aging:
Recent studies using genetically modified mice, such as FGF23-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan.
… after the Second World War in Europe especially in Germany and DDR, children received extremely high oral doses of vitamin D and suffered hypercalcemia, early aging, cardiovascular complications and early death suggesting that hypervitaminosis D can accelerate aging. (Tuohimaa 2009)
References
Frost, P. (2009). Black-White differences in cancer risk and the vitamin-D hypothesis, Journal of the National Medical Association, 101, 1310-1313.
Mekel-Bobrov, N., Posthuma D., Gilbert S.L., et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mole Genet, 16, 600–8.
Rejnmark L, Jørgensen ME, Pedersen MB, et al. (2004). Vitamin D insufficiency in Greenlanders on a Westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes, Calcif Tissue Int, 74, 255-263.
Rushton, J.P., Vernon, PA.., Bons, T.A. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism. Biology Letters-UK, 3, 157–60.
Sellers EAC, Sharma A, Rodd C. (2003). Adaptation of Inuit children to a low-calcium diet, Canadian Medical Association Journal, 168, 1141-1143.
Tuohimaa, P. (2009). Vitamin D and aging, Journal of Steroid Biochemistry and Molecular Biology, 114, 78-84.
