Highlights of the 2013 IID. Part 1: Evolution and filaggrin mutations vs. vitamin D production

Did latitude-dependent differences in prevalence of filaggrin mutations evolve to support cutaneous vitamin D production? JP Thyssen and PM Elias.

Skin became more lightly pigmented when modern humans migrated northward out of Africa into Europe and Asia. Evolutionary biologists increasingly accept the hypothesis that pigmentation lightened in order to allow more ultraviolet light to enter the skin, where it can then stimulate the formation of additional vitamin D.

In a recent article in the Journal of Human Evolution, we provided many reasons why this hypothesis is flawed and suggested instead that pigment dilution developed as a form of ‘metabolic conservation’. While abundant pigment was needed to protect our skin from the intense ultraviolet light of equatorial Africa, it was no longer needed in the weaker light of the higher latitudes. Hence, mutations arising in the genes for pigment-producing proteins that reduced pigmentation were retained, because they allowed skin to divert energy towards other, more urgent requirements.

In addition to genes diluting pigmentation, these early European hunter-gatherers, as they migrated further northward behind retreating glaciers less than 10,000 years ago, developed mutations in the gene encoding filaggrin. This epidermal protein is metabolized to urocanic acid (UCA) in the outermost layer of skin, the stratum corneum.  UCA is the most potent sunscreen molecule in lightly-pigmented individuals, perhaps even more important for this function than melanin in this population. Hence, mutations resulting in the loss of  filaggrin-derived UCA would permit more UV-B to enter the skin, where it could stimulate epidermal vitamin D production.

Importantly, the frequency of filaggrin mutations is highest precisely in European populations of the far north, who would have been at greatest risk for vitamin D deficiency. Seafood or other dietary sources of vitamin D was not a prominent part of the diet in these populations who subsisted on reindeer and other cold-adapted fauna, in marked contrast to the fish-enriched diet of Inuits and other northern Eurasian peoples. The circulating blood levels of vitamin D in northern Europeans is higher than in more southern populations, despite their residence at latitudes comparable to Alaska and Labrador in the Western hemisphere.

When we correlated the reported frequency of filaggrin gene mutations with vitamin D blood levels at various latitudes within Europe, we found an almost perfect (inverse) correlation.  These populations we propose found the loss of the benefits of filaggrin on the skin barrier a small price to pay in order to ensure sufficient vitamin D production during summer months that could sustain them through the long dark winters. It was only with the advent of contemporary urbanization that the cost of a weaker skin barrier, with its increasing frequency of atopic dermatitis and other atopic diseases like asthma, came to the fore.

Bottom Line: It has been puzzling why filaggrin mutations are so common among people of northern European ancestry, because they predispose to severe atopic dermatitis and even asthma.  These observations suggest that they may have evolved as a trade-off to prevent vitamin D deficiency in these far northern climes.  Because allergic diseases likely were not prevalent until very recently in human history, this cost is only now being realized.