Recent evidence suggests that a non-pigmentation mutation of the epidermal structural protein filaggrin (FLG) better explains how populations in northern latitudes, namely northern Europeans, compensate for lower levels of ultraviolet-B light exposure (1).
Scientists from the University of San Francisco compiled loss-of-function FLG mutation prevalence data from various populations and found that northern Europeans demonstrated a significantly higher rate of loss-of-function FLG mutations (1).
FLG strongly correlates to cutaneous vitamin D3 production, a process catalyzed by ultraviolet-B rays from the sun. Vitamin D3 plays a crucial role in maintaining bone health and various metabolic and immune processes. However, people who live farther from the equator (i.e. north) receive less ultraviolet-B light exposure (1).
FLG is normally converted into trans-urocanic acid, which absorbs ultraviolet-B rays in outer layers of the epidermis. Loss of the FLG gene results in increased vitamin D3 production, an effect seen most strikingly in northern Europeans (1).
According to the data, northern Europeans, such as those from Sweden, Germany, and the United Kingdom, demonstrate an average loss-of-function FLG mutation prevalence of 8.3%. Compared to their southern European counterparts’ average prevalence of 3.5%, the data reveals a significant north-to-south latitude gradient (1).
Africans, who, of the examined populations, are one of the closest to the equator, had a near-zero rate of loss-of-function FLG mutation prevalence (1).
Although the loss of FLG leads to dry skin and increased risk of asthma and food allergies, Elias and his team believe that, at the time, the benefits of increased vitamin D3 production outweighed the negative side effects of the mutation (1).
Until recently, most people accepted the theory that northerners compensated for lower levels of ultraviolet-B exposure by decreasing production of the skin pigment melanin. However, Elias and his team believe that several key pieces of evidence refute this theory (1).
First, mutations in genes regulating skin pigmentation did not reveal any north-to-south pattern as the FLG mutation did. Additionally, human fossils from the late Pleistocene and early Holocene era, before significant melanin production loss, did not reveal rickets or other signs of bone weakening. In fact, dark-skinned populations had lower rates of osteoporosis (1).
Other pieces of crucial evidence include that loss of pigmentation did not occur in a way that would best promote vitamin D3 production. Humans lost pigmentation in areas where no advantage was conferred, such as hair follicles, but did not develop any pattern of pigmentation based on skin exposure to the sun (1).
Elias and his team suggest that melanin metabolism may have been lost to conserve energy rather than for vitamin D3 production, as melanin was no longer as required as protection from ultraviolet-B rays (1).
Elias and his team believe that the next steps require additional data from Inuits and other northern Asian populations with significant melanin pigmentation. If the Inuit people have low FLG mutation prevalence, the theory will be supported and would suggest that the vitamin D3-rich, seafood-based diet of the Inuit people negates the need for greater ultraviolet-B exposure (1).
Based on the prevalence of loss-of-function Filaggrin (FLG) mutations in various populations, scientists theorize that a mutation in the FLG gene, rather than the pigment melanin, best explains how northerners, who receive less ultraviolet-B light, produce adequate vitamin D3.
References
(1) J. P. Thyssen, D. D. Bikle, P. M. Elias. Evidence that loss-of-function filaggrin gene mutations evolved in Northern Europeans to favor intracutaneous vitamin D3 production. Evolutionary Biology, (2014), doi:10.1007/s11692-014-9282-7