Light skin

A Norwegian woman with light skin

Light skin is a human skin color that has a low level of eumelanin pigmentation as an adaptation to environments of low UV radiation. ^{[1] [2] [3]} Light skin is most commonly found amongst the native populations of Europe, West Asia, Central Asia, and Northeast Asia as measured through skin reflectance. ^[4] People with light skin pigmentation are often referred to as "white" ^{[5] [6]} although these usages can be ambiguous in some countries where they are used to refer specifically to certain ethnic groups or populations. ^[7]

Humans with light skin pigmentation have skin with low amounts of eumelanin, and possess fewer melanosomes than humans with dark skin pigmentation. Light skin provides better absorption qualities of ultraviolet radiation, which helps the body to synthesize higher amounts of vitamin D for bodily processes such as calcium development. ^{[3] [8]} On the other hand, light-skinned people who live near the equator, where there is abundant sunlight, are at an increased risk of folate depletion. As a consequence of folate depletion, they are at a higher risk of DNA damage, birth defects, and numerous types of cancers, especially skin cancer. ^[9] Humans with darker skin who live further from the tropics may have lower vitamin D levels, which can also lead to health complications, both physical and mental, including a greater risk of developing schizophrenia. ^[10] These two observations form the "vitamin D–folate hypothesis", which attempts to explain why populations that migrated away from the tropics into areas of low UV radiation ^[11] evolved to have light skin pigmentation. ^{[3] [12] [13]}

The distribution of light-skinned populations is highly correlated with the low ultraviolet radiation levels of the regions inhabited by them. Historically, light-skinned populations almost exclusively lived far from the equator, in high latitude areas with low sunlight intensity. ^[14] Due to colonization, imperialism, and increased mobility of people between geographical regions in recent centuries, light-skinned populations today are found all over the world. ^{[3] [15]}

Evolution

History of human pigmentation in Europe (with Asia geographic extension). Scandinavian hunter-gatherers had higher levels of light pigmentation variants compared to their ancestors from other parts of Europe, suggesting adaptation to low light conditions. Some authors have expressed caution regarding the skin pigmentation predictions.

It is generally accepted that dark skin evolved as a protection against the effect of UV radiation; eumelanin protects against both folate depletion and direct damage to DNA. ^{[3] [18] [19] [20]} This accounts for the dark skin pigmentation of Homo sapiens during their development in Africa; the major migrations out of Africa to colonize the rest of the world were also dark-skinned. ^[21] It is widely supposed that light skin pigmentation developed due to the importance of maintaining vitamin D3 production in the skin. ^[22] Strong selective pressure would be expected for the evolution of light skin in areas of low UV radiation. ^[12]

After the ancestors of West Eurasians and East Eurasians diverged more than 40,000 years ago, lighter skin tones evolved independently in a subset of each of the two populations. In West Eurasians, the A111T allele of the rs1426654 polymorphism in the pigmentation gene SLC24A5 has the largest skin lightening effect and is widespread in Europe, South Asia, Central Asia, the Near East and North Africa. ^[23]

In a 2013 study, Canfield et al. established that SLC24A5 sits in a block of haplotypes, one of which (C11) is shared by virtually all chromosomes that bear the A111T variant. This "equivalence" between C11 and A111T indicates that all people who carry this skin-lightening allele descend from a common origin: a single carrier who lived most likely "between the Middle East and the Indian subcontinent". Canfield et al. attempted to date the A111T mutation but only constrained the age range to before the Neolithic. ^[23] However, a second study from the same year (Basu Mallick et al.) estimated the coalescent age (split date) for this allele to between ~28,000 and ~22,000 years ago. ^[24]

The second most important skin-lightening factor in West Eurasians is the depigmenting allele F374 of the rs16891982 polymorphism located in the melanin-synthesis gene SLC45A2. From its low haplotype diversity, Yuasa et al. (2006) likewise concluded that this mutation (L374F) "occurred only once in the ancestry of Caucasians". ^[25]

Summarising these studies, Hanel and Carlberg (2020) decided that the alleles of the two genes SLC24A5 and SLC45A2 which are most associated with lighter skin colour in modern Europeans originated in West Asia about 22,000 to 28,000 years ago and these two mutations each arose in a single carrier. ^[21] This is consistent with Jones et al. (2015), who reconstructed the relationship between Near Eastern Neolithic farmers and Caucasus Hunter-Gatherers: two populations which carried the light skin variant of SLC24A5. Analysing newly sequenced ancient genomes, Jones et al. estimated the split date at ~24,000 bp and localised the separation to somewhere south of the Caucasus. ^[26] However, a coalescent analysis of this allele by Crawford et al. (2017) gave a more narrowly constrained, and earlier, split date of ~29,000 years ago (with a 95% confidence window from 28,000 to 31,000 bp). ^[27]

The light skin variants of SLC24A5 and SLC45A2 were present in Anatolia by 9,000 years ago, where they became associated with the Neolithic Revolution. From here, their carriers spread Neolithic farming across Europe. ^[28] Lighter skin and blond hair also evolved in the Ancient North Eurasian population. ^[29]

A further wave of lighter-skinned populations across Europe (and elsewhere) is associated with the Yamnaya culture and the Indo-European migrations bearing Ancient North Eurasian ancestry and the KITLG allele for blond hair. Furthermore, the SLC24A5 gene linked with light pigmentation in Europeans was introduced into East Africa from Europe over five thousand years ago. These alleles can now be found in the San, Ethiopians, and Tanzanian populations with Afro-Asiatic ancestry. ^{[23] [30] [31]} The SLC24A5 in Ethiopia maintains a substantial frequency with Semitic and Cushitic speaking populations, compared with Omotic, Nilotic or Niger-Congo speaking groups. It is inferred that it may have arrived into the region via migration from the Levant, which is also supported by linguistic evidence. ^[32] In the San people, it was acquired from interactions with Eastern African pastoralists. ^[33] Meanwhile, in the case of north-east Asia and the Americas, a variation of the MFSD12 gene is responsible for lighter skin colour. ^[29] The modern association between skin tone and latitude is thus a relatively recent development. ^[21]

Some authors have expressed caution regarding the skin pigmentation predictions. According to Ju et al. (2021), in a study addressing 40,000 years of modern human history, "we can assess the extent to which they carried the same light pigmentation alleles that are present today", but explain that c. 40,000 BP Early Upper Paleolithic hunter-gatherers "may have carried different alleles that we cannot now detect", and as a result "we cannot confidently make statements about the skin pigmentation of ancient populations.” ^[17]

According to Crawford et al. (2017), most of the genetic variants associated with light and dark pigmentation appear to have originated more than 300,000 years ago. ^[34] African, South Asian and Australo-Melanesian populations also carry derived alleles for dark skin pigmentation that are not found in Europeans or East Asians. ^[30] Huang et al. 2021 found the existence of "selective pressure on light pigmentation in the ancestral population of Europeans and East Asians", prior to their divergence from each other. Skin pigmentation was also found to be affected by directional selection towards darker skin among Africans, as well as lighter skin among Eurasians. ^[35] Crawford et al. (2017) similarly found evidence for selection towards light pigmentation prior to the divergence of West Eurasians and East Asians. ^[30]

A study conducted by Fregel, Rosa et al. (2018), showed that Late Neolithic Moroccans had the European derived SLC24A5 mutation and other alleles that predispose individuals to lighter skin and eye colour. ^[36] The A111T mutation in the SLC24A5 gene predominates in populations with Western Eurasian ancestry. The geographical distribution shows that it is nearly fixed in all of Europe and most of the Middle East, extending east to some populations in present-day Pakistan and Northern India. It shows a latitudinal decline toward the Equator, with high frequencies in North Africa (80%), and intermediate (40−60%) in Ethiopia and Somalia. ^[23]

Geographic distribution; ultraviolet and vitamin D

Skin reflectance vs. latitude

Some people in Mongolia and Manchuria have light skin.

In the 1960s, biochemist W. Farnsworth Loomis suggested that skin colour is related to the body's need for vitamin D. The major positive effect of UV radiation in land-living vertebrates is the ability to synthesize vitamin D3 from it. A certain amount of vitamin D helps the body to absorb more calcium which is essential for building and maintaining bones, especially for developing embryos. Vitamin D production depends on exposure to sunlight. Humans living at latitudes far from the equator developed light skin in order to help absorb more vitamin D. People with light (type II) skin can produce previtamin D3 in their skin at rates 5–10 times faster than dark-skinned (type V) people. ^{[37] [38] [39] [40] [41]}

In 1998, anthropologist Nina Jablonski and her husband George Chaplin collected spectrometer data to measure UV radiation levels around the world and compared it to published information on the skin colour of indigenous populations of more than 50 countries. The results showed a very high correlation between UV radiation and skin colour; the weaker the sunlight was in a geographic region, the lighter the indigenous people's skin tended to be. Jablonski points out that people living above the latitudes of 50 degrees have the highest chance of developing vitamin D deficiency. She suggests that people living far from the equator developed light skin to produce adequate amounts of vitamin D during winter with low levels of UV radiation. Genetic studies suggest that light-skinned humans have been selected for multiple times. ^{[42] [43] [44]}

Some people in Afghanistan and Pakistan have light skin.

Polar regions, vitamin D, and diet

A light-skinned Assyrian woman.

Polar regions of the Northern Hemisphere receive little UV radiation, and even less vitamin D-producing UVB, for most of the year. These regions were uninhabited by humans until about 12,000 years ago. (In northern Fennoscandia at least, human populations arrived soon after deglaciation.) ^[45] Areas like Scandinavia and Siberia have very low concentrations of ultraviolet radiation, and indigenous populations are all light-skinned. ^{[3] [38]}

However, dietary factors may allow vitamin D sufficiency even in dark skinned populations. ^{[46] [47]} Many indigenous populations across Northern Europe and Northern Asia survive by consuming reindeer, which they follow and herd. Reindeer meat, organs, and fat contain large amounts of vitamin D which the reindeer get from eating substantial amounts of lichen. ^[48] Some people of the polar regions, like the Inuit (Eskimos), retained their dark skin; they ate Vitamin D-rich seafood, such as fish and sea mammal blubber. ^[49]

Furthermore, these people have been living in the far north for less than 7,000 years. As their founding populations lacked alleles for light skin colour, they may have had insufficient time for significantly lower melanin production to have been selected for by nature after being introduced by random mutations. ^[50] "This was one of the last barriers in the history of human settlement," Jablonski states. "Only after humans learned fishing, and therefore had access to food rich in vitamin D, could they settle regions of high latitude." Additionally, in the spring, Inuit would receive high levels of UV radiation as reflection from the snow, and their relatively darker skin then protects them from the sunlight. ^{[3] [12] [8]}

Earlier hypotheses

Two other main hypotheses have been put forward to explain the development of light skin pigmentation: resistance to cold injury, and genetic drift; now both of them are considered unlikely to be the main mechanism behind the evolution of light skin. ^[3]

The resistance to cold injury hypothesis claimed that dark skin was selected against in cold climates far from the equator and in higher altitudes as dark skin was more affected by frostbite. ^[51] It has been found that reaction of the skin to extreme cold climates has actually more to do with other aspects, such as the distribution of connective tissue and distribution of fat, ^{[52] [53]} and with the responsiveness of peripheral capillaries to differences in temperature, and not with pigmentation. ^[3]

The supposition that dark skin evolved in the absence of selective pressure was put forward by the probable mutation effect hypothesis. ^[54] The main factor initiating the development of light skin was seen as a consequence of genetic mutation without an evolutionary selective pressure. The subsequent spread of light skin was thought to be caused by assortive mating ^[53] and sexual selection contributed to an even lighter pigmentation in females. ^{[55] [56]} Doubt has been cast on this hypothesis, as more random patterns of skin colouration would be expected in contrast to the observed structural light skin pigmentation in areas of low UV radiation. ^[44] The clinal (gradual) distribution of skin pigmentation observable in the Eastern hemisphere, and to a lesser extent in the Western hemisphere, is one of the most significant characteristics of human skin pigmentation. Increasingly lighter skinned populations are distributed across areas with incrementally lower levels of UV radiation. ^{[57] [58]}

Genetic associations

Variations in the KITL gene have been positively associated with about 20% of melanin concentration differences between African and non-African populations. One of the alleles of the gene has an 80% occurrence rate in Eurasian populations. ^{[59] [60]} The ASIP gene has a 75–80% variation rate among Eurasian populations compared to 20–25% in African populations. ^[61] Variations in the SLC24A5 gene account for 20–25% of the variation between dark and light skinned populations of Africa, ^[62] and appear to have arisen as recently as within the last 10,000 years. ^[63] The Ala111Thr or rs1426654 polymorphism in the coding region of the SLC24A5 gene reaches fixation in Europe, but is found across the globe, particularly among populations in Northern Africa, the Horn of Africa, West Asia, Central Asia and South Asia. ^{[64] [65] [66]}

Biochemistry

Melanin is a derivative of the amino acid tyrosine. Eumelanin is the dominant form of melanin found in human skin. Eumelanin protects tissues and DNA from radiation damage by UV light. Melanin is produced in specialized cells called melanocytes, which are found in the lowest level of the epidermis. ^[67] Melanin is produced inside small membrane-bound packages called melanosomes. Humans with naturally occurring light skin have varied amounts of smaller and sparsely distributed eumelanin and its lighter-coloured relative, pheomelanin. ^{[42] [68]} The concentration of pheomelanin varies highly within populations from individual to individual, but it is more commonly found among lightly pigmented Europeans, East Asians, and Native Americans. ^{[22] [69]}

For the same body region, individuals, independently of skin colour, have the same amount of melanocytes (however variation between different body parts is substantial), but organelles which contain pigments, called melanosomes, are smaller and less numerous in light-skinned humans. ^[70]

For people with very light skin, the skin gets most of its colour from the bluish-white connective tissue in the dermis and from the haemoglobin associated blood cells circulating in the capillaries of the dermis. The colour associated with the circulating haemoglobin becomes more obvious, especially in the face, when arterioles dilate and become tumefied with blood as a result of prolonged physical exercise or stimulation of the sympathetic nervous system (usually embarrassment or anger). ^[71] Up to 50% of UVA can penetrate deeply into the dermis in persons with light skin pigmentation with little protective melanin pigment. ^[48]

The combination of light skin, red hair, and freckling is associated with high amount of pheomelanin, little amounts of eumelanin. This phenotype is caused by a loss-of-function mutation in the melanocortin 1 receptor (MC1R) gene. ^{[72] [73]} However, variations in the MC1R gene sequence only have considerable influence on pigmentation in populations where red hair and extremely light skin is prevalent. ^[44] The gene variation's primary effect is to promote eumelanin synthesis at the expense of pheomelanin synthesis, although this contributes to very little variation in skin reflectance between different ethnic groups. ^[74] Melanocytes from light skin cells cocultured with keratinocytes give rise to a distribution pattern characteristic of light skin. ^[75]

Freckles usually only occur in people with very lightly pigmented skin. They vary from very dark to brown in colour and develop a random pattern on the skin of the individual. ^[76] Solar lentigines, the other types of freckles, occur among old people regardless of skin colour. ^[3] People with very light skin (types I and II) make very little melanin in their melanocytes, and have very little or no ability to produce melanin in the stimulus of UV radiation. ^[77] This can result in frequent sunburns and a more dangerous, but invisible, damage done to connective tissue and DNA underlying the skin. This can contribute to premature aging and skin cancer. ^{[78] [79]} The strongly red appearance of lightly pigmented skin as a response to high UV radiation levels is caused by the increased diameter, number, and blood flow of the capillaries. ^[22]

People with moderately pigmented skin (Types III-IV) are able to produce melanin in their skin in response to UVR. Normal tanning is usually delayed as it takes time for the melanins to move up in the epidermis. Heavy tanning does not approach the photoprotective effect against UVR-induced DNA damage compared to naturally occurring dark skin, ^{[80] [81]} however it offers great protection against seasonal variations in UVR. Gradually developed tan in the spring prevents sunburns in the summer. This mechanism is almost certainly the evolutionary reason behind the development of tanning behaviour. ^[3]

Health implications

Skin pigmentation is an evolutionary adaptation to the various UV radiation levels around the world. There are health implications of light-skinned people living in environments of high UV radiation. Various cultural practices increase problems related to health conditions of light skin, for example sunbathing among the light-skinned. ^[3]

Advantages in low sunlight

Humans with light skin pigmentation living in low sunlight environments experience increased vitamin D synthesis compared to humans with dark skin pigmentation due to the ability to absorb more sunlight. Almost every part of the human body, including the skeleton, the immune system, and brain requires vitamin D. Vitamin D production in the skin begins when UV radiation penetrates the skin and interacts with a cholesterol-like molecule produce pre-vitamin D3. This reaction only occurs in the presence of medium length UVR, UVB. Most of the UVB and UVC rays are destroyed or reflected by ozone, oxygen, and dust in the atmosphere. UVB reaches the Earth's surface in the highest amounts when its path is straight and goes through a little layer of atmosphere.

The farther a place is from the equator, the less UVB is received, and the potential to produce of vitamin D is diminished. Some regions far from the equator do not receive UVB radiation at all between autumn and spring. ^[48] Vitamin D deficiency does not kill its victims quickly, and generally does not kill at all. Rather it weakens the immune system, the bones, and compromises the body's ability to fight uncontrolled cell division which results in cancer. A form of vitamin D is a potent cell growth inhibitor; thus chronic deficiencies of vitamin D seem to be associated with higher risk of certain cancers. This is an active topic of cancer research and is still debated. ^[48] The vitamin D deficiency associated with dark skin leads to higher levels of schizophrenia in such populations residing in northerly latitudes. ^[82]

With the increase of vitamin D synthesis, there is a decreased incidence of conditions that are related to common vitamin D deficiency conditions of people with dark skin pigmentation living in environments of low UV radiation: rickets, osteoporosis, numerous cancer types (including colon and breast cancer), and immune system malfunctioning. Vitamin D promotes the production of cathelicidin, which helps to defend humans' bodies against fungal, bacterial, and viral infections, including flu. ^{[3] [15]} When exposed to UVB, the entire exposed area of body's skin of a relatively light skinned person is able to produce between 10 and 20000 IU of vitamin D. ^[48]

Disadvantages in high sunlight

Fatal neural tube defect with evident anencephaly.

Light-skinned people living in high sunlight environments are more susceptible to the harmful UV rays of sunlight because of the lack of melanin produced in the skin. The most common risk that comes with high exposure to sunlight is the increased risk of sunburns. This increased risk has come along with the cultural practice of sunbathing, which is popular among light-skinned populations. This cultural practice to gain tanned skin if not regulated properly can lead to sunburn, especially among very lightly-skinned humans. The overexposure to sunlight also can lead to basal cell carcinoma, which is a common form of skin cancer.

Another health implication is the depletion of folate within the body, where the overexposure to UV light can lead to megaloblastic anemia. Folate deficiency in pregnant women can be detrimental to the health of their newborn babies in the form of neural tube defects, miscarriages, and spina bifida, a birth defect in which the backbone and spinal canal do not close before birth. ^[83] The peak of neural tube defect occurrences is the highest in the May–June period in the Northern Hemisphere. ^[3] Folate is needed for DNA replication in dividing cells and deficiency can lead to failures of normal embryogenesis and spermatogenesis. ^{[3] [15] [38]}

Individuals with lightly pigmented skin who are repeatedly exposed to strong UV radiation, experience faster aging of the skin, which shows in increased wrinkling and anomalies of pigmentation. Oxidative damage causes the degradation of protective tissue in the dermis, which confers the strength of the skin. ^[22] It has been postulated that white women may develop wrinkles faster than black women after menopause because white women are more susceptible to sun damage throughout life. Dr. Hugh S. Taylor, of Yale School of Medicine, concluded that the study could not prove the findings but they suspect the underlying cause. Light-coloured skin has been suspected to be one of the contributing factors that promote wrinkling. ^{[84] [85]}

See also

• Dark skin
• Olive skin
• High yellow
• Skin whitening
• Blond
• Red hair
• Albinism in humans

References

1. light-skinned Princeton University
2. "Light-skinned". thefreedictionary.com. Retrieved 24 January 2017.
3. Muehlenbein, Michael (2010). Human Evolutionary Biology . Cambridge University Press. pp.  192–213.
4. Relethford, John (1997). Fundamentals of Biological Anthropology. Mayfield Publishing Company. p. 270. ISBN   978-1559346672.
5. Oxford Dictionaries. April 2010. Oxford University Press. "belonging to or denoting a human group having light-coloured skin" "white" (accessed 6 August 2012).
6. Dictionary.com: white 3.a "marked by slight pigmentation of the skin"
7. "Global Census". American Anthropological Association. Archived from the original on 14 September 2018. Retrieved 10 December 2012.
8. Kirchweger, Gina. "The Biology of Skin Color: Black and White". Evolution Library. PBS. Retrieved 22 September 2018.
9. Wolf, S. Tony; Kenney, W. Larry (1 September 2019). "The vitamin D-folate hypothesis in human vascular health". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 317 (3). American Physiological Society: R491–R501. doi: 10.1152/ajpregu.00136.2019 . ISSN   0363-6119. PMC   6766707 .
10. Cui, Xiaoying; J. McGrath, John; H. J. Burne, Thomas (26 January 2021). "Vitamin D and schizophrenia: 20 years on". Nature. 26 (7): 2708–2720. doi:10.1038/s41380-021-01025-0. PMC   8505257 . PMID   33500553.
11. Appenzeller, Tim (2012). "Human migrations: Eastern odyssey". Nature. 485 (7396): 24–26. Bibcode:2012Natur.485...24A. doi: 10.1038/485024a . PMID   22552074.
12. Relethford, JH (2000). "Human skin color diversity is highest in sub-Saharan African populations". Human Biology; an International Record of Research. 72 (5): 773–80. PMID   11126724.
13. Jones, P.; Lucock, M.; Veysey, M.; Beckett, E. (2018). "The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas". Nutrients. 10 (5): 554. doi: 10.3390/nu10050554 . PMC   5986434 . PMID   29710859.
14. "Modern human variation: overview". Archived from the original on 5 November 2012.
15. O'Neil, Dennis. "Skin Color Adaptation". Human Biological Adaptability: Skin Color as an Adaptation. Palomar. Archived from the original on 18 December 2012. Retrieved 10 December 2012.
16. Günther, Torsten; Malmström, Helena; Svensson, Emma M.; Omrak, Ayça; Sánchez-Quinto, Federico; Kılınç, Gülşah M.; Krzewińska, Maja; Eriksson, Gunilla; Fraser, Magdalena; Edlund, Hanna; Munters, Arielle R. (9 January 2018). "Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation". PLOS Biology. 16 (1). From supporting information document S8, page 5/28. doi: 10.1371/journal.pbio.2003703 . ISSN   1545-7885. PMC   5760011 . PMID   29315301. However, for all three well-characterized skin and eye-color associated SNPs, the SHGs display a frequency that is greater for the light-skin variants and the blue-eye variant than can be expected from a mixture of WHGs and EHGs. This observation indicates that the frequencies may have increased due to continued adaptation to a low light conditions.
17. Ju, Dan; Mathieson, Ian (2021). "The evolution of skin pigmentation-associated variation in West Eurasia". PNAS. 118 (1): e2009227118. Bibcode:2021PNAS..11809227J. doi: 10.1073/pnas.2009227118 . PMC   7817156 . PMID   33443182. Relatively dark skin pigmentation in Early Upper Paleolithic Europe would be consistent with those populations being relatively poorly adapted to high-latitude conditions as a result of having recently migrated from lower latitudes. On the other hand, although we have shown that these populations carried few of the light pigmentation alleles that are segregating in present-day Europe, they may have carried different alleles that we cannot now detect.
18. Vieth, Reinhold (2003). "Effects of Vitamin D on bone and natural selection of skin color: How much vitamin D nutrition are we talking about?". In Agarwal, Sabrina C.; Stout, Samuel D. (eds.). Bone loss and osteoporosis: An anthropological perspective. New York City: Kluwer Academic / Plenum Press. pp. 139–154. doi:10.1007/978-1-4419-8891-1_9. ISBN   978-0-306-47767-6.
19. Hatchcock, J. N.; Shao, A.; Vieth, R.; Heaney, R.; et al. (2007). "Risk assessment for vitamin D". American Journal of Clinical Nutrition . 72 (1): 451–462. doi: 10.1093/ajcn/85.1.6 . PMID   17209171.
20. Kimball, Samantha; Fuleihan, Ghada El-Hajj; Vieth, Reinhold (2008). "Vitamin D: A growing perspective". Critical Reviews in Clinical Laboratory Sciences . 45 (4): 339–414. doi:10.1080/10408360802165295. ISSN   1040-8363. PMID   18568854. S2CID   57808076.
21. Hanel, Andrea; Carlberg, Carsten (2020). "Skin colour and vitamin D: An update". Experimental Dermatology. 29 (9): 864–875. doi: 10.1111/exd.14142 . PMID   32621306. S2CID   220335539.
22. Jablonski, Nina G. (October 2004). "The evolution of human skin and skin color". Annual Review of Anthropology. 33 (1): 585–623. doi:10.1146/annurev.anthro.33.070203.143955. ISSN   0084-6570.
23. Canfield, Victor A.; Berg, Arthur; Peckins, Steven; Wentzel, Steven M.; Ang, Khai Chung; Oppenheimer, Stephen; Cheng, Keith C. (1 November 2013). "Molecular Phylogeography of a Human Autosomal Skin Color Locus Under Natural Selection". G3: Genes, Genomes, Genetics . 3 (11): 2059–2067. doi:10.1534/g3.113.007484. ISSN   2160-1836. PMC   3815065 . PMID   24048645.
24. Basu Mallick, Chandana; Iliescu, Florin Mircea; Möls, Märt; Hill, Sarah; Tamang, Rakesh; Chaubey, Gyaneshwer; Goto, Rie; Ho, Simon Y. W.; Gallego Romero, Irene; Crivellaro, Federica; Hudjashov, Georgi; Rai, Niraj; Metspalu, Mait; Mascie-Taylor, C. G. Nicholas; Pitchappan, Ramasamy; Singh, Lalji; Mirazon-Lahr, Marta; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas (7 November 2013). "The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent". PLoS Genetics. 9 (11): e1003912. doi: 10.1371/journal.pgen.1003912 . ISSN   1553-7404. PMC   3820762 . PMID   24244186.
25. Yuasa, I.; Umetsu, K.; Harihara, S.; Kido, A.; Miyoshi, A.; Saitou, N.; Dashnyam, B.; Jin, F.; Lucotte, G.; Chattopadhyay, P.K.; Henke, L.; Henke, J. (November 2006). "Distribution of the F374 Allele of the SLC45A2 (MATP) Gene and Founder-Haplotype Analysis". Annals of Human Genetics. 70 (6): 802–811. doi:10.1111/j.1469-1809.2006.00261.x. ISSN   0003-4800. PMID   17044855.
26. Jones, Eppie R.; Gonzalez-Fortes, Gloria; Connell, Sarah; Siska, Veronika; Eriksson, Anders; Martiniano, Rui; McLaughlin, Russell L.; Gallego Llorente, Marcos; Cassidy, Lara M.; Gamba, Cristina; Meshveliani, Tengiz; Bar-Yosef, Ofer; Müller, Werner; Belfer-Cohen, Anna; Matskevich, Zinovi; Jakeli, Nino; Higham, Thomas F. G.; Currat, Mathias; Lordkipanidze, David; Hofreiter, Michael; Manica, Andrea; Pinhasi, Ron; Bradley, Daniel G. (16 November 2015). "Upper Palaeolithic genomes reveal deep roots of modern Eurasians". Nature Communications. 6 (1). doi:10.1038/ncomms9912. ISSN   2041-1723. PMC   4660371 . PMID   26567969.
27. Crawford, Nicholas G.; Kelly, Derek E.; Hansen, Matthew E. B.; Beltrame, Marcia H.; Fan, Shaohua; Bowman, Shanna L.; Jewett, Ethan; Ranciaro, Alessia; Thompson, Simon; Lo, Yancy; Pfeifer, Susanne P.; Jensen, Jeffrey D.; Campbell, Michael C.; Beggs, William; Hormozdiari, Farhad; Mpoloka, Sununguko Wata; Mokone, Gaonyadiwe George; Nyambo, Thomas; Meskel, Dawit Wolde; Belay, Gurja; Haut, Jake; NISC Comparative Sequencing Program; Rothschild, Harriet; Zon, Leonard; Zhou, Yi; Kovacs, Michael A.; Xu, Mai; Zhang, Tongwu; Bishop, Kevin; Sinclair, Jason; Rivas, Cecilia; Elliot, Eugene; Choi, Jiyeon; Li, Shengchao A.; Hicks, Belynda; Burgess, Shawn; Abnet, Christian; Watkins-Chow, Dawn E.; Oceana, Elena; Song, Yun S.; Eskin, Eleazar; Brown, Kevin M.; Marks, Michael S.; Loftus, Stacie K.; Pavan, William J.; Yeager, Meredith; Chanock, Stephen; Tishkoff, Sarah A. (17 November 2017). "Loci associated with skin pigmentation identified in African populations". Science. 358 (6365). doi:10.1126/science.aan8433. ISSN   0036-8075. PMC   5759959 . PMID   29025994. On the basis of coalescent analysis with sequence data from the Simons Genomic Diversity Project (SGDP), the time to most recent common ancestor (TMRCA) of most Eurasian lineages containing the rs1426654 (A) allele is 29 thousand years ago (ka) [95% critical interval (CI), 28 to 31 ka], consistent with previous studies.
28. Paschou, Peristera; Drineas, Petros; Yannaki, Evangelia; Razou, Anna; Kanaki, Katerina; Tsetsos, Fotis; Padhmanabuni, Shanmukha; Michalodimitrakis, Manolis; Renda, Maria; Pavolovic, Sonja; Anagnostopoulos, Achilles; Stamatoyannopoulos, John; Kidd, Kenneth; Stamatoyannopoulos, George (24 June 2014). "Maritime route of colonization of Europe". Proceedings of the National Academy of Sciences of the United States of America. 111 (25): 9211–9216. Bibcode:2014PNAS..111.9211P. doi: 10.1073/pnas.1320811111 . PMC   4078858 . PMID   24927591.
29. Downes, Natasha (21 January 2019). "Genetic study provides novel insights into the evolution of skin colour". UCL News (Press release). University College London. Retrieved 4 December 2021.
30. Crawford, Nicholas G.; Kelly, Derek E.; Hansen, Matthew E. B.; Beltrame, Marcia H.; Fan, Shaohua; Bowman, Shanna L.; Jewett, Ethan; Ranciaro, Alessia; Thompson, Simon; Lo, Yancy; Pfeifer, Susanne P.; Jensen, Jeffrey D.; Campbell, Michael C.; Beggs, William; Hormozdiari, Farhad (17 November 2017). "Loci associated with skin pigmentation identified in African populations". Science. 358 (6365): eaan8433. doi:10.1126/science.aan8433. ISSN   1095-9203. PMC   5759959 . PMID   29025994.
31. Feng, Yuanqing; McQuillan, Michael A.; Tishkoff, Sarah A. (26 April 2021). "Evolutionary genetics of skin pigmentation in African populations". Human Molecular Genetics. 30 (R1): R88–R97. doi:10.1093/hmg/ddab007. ISSN   1460-2083. PMC   8117430 . PMID   33438000.
32. Pagani, Luca; Kivisild, Toomas; Tarekegn, Ayele; Ekong, Rosemary; Plaster, Chris; Gallego Romero, Irene; Ayub, Qasim; Mehdi, S. Qasim; Thomas, Mark G.; Luiselli, Donata; Bekele, Endashaw (13 July 2012). "Ethiopian genetic diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool". American Journal of Human Genetics. 91 (1): 83–96. doi:10.1016/j.ajhg.2012.05.015. ISSN   1537-6605. PMC   3397267 . PMID   22726845.
33. Lin, Meng; Siford, Rebecca L.; Martin, Alicia R.; Nakagome, Shigeki; Möller, Marlo; Hoal, Eileen G.; Bustamante, Carlos D.; Gignoux, Christopher R.; Henn, Brenna M. (26 December 2018). "Rapid evolution of a skin-lightening allele in southern African KhoeSan". Proceedings of the National Academy of Sciences of the United States of America. 115 (52): 13324–13329. Bibcode:2018PNAS..11513324L. doi: 10.1073/pnas.1801948115 . ISSN   1091-6490. PMC   6310813 . PMID   30530665.
34. Baillie, Katherine Unger (12 October 2017). "Genes responsible for diversity of human skin colors identified". Penn Today (Press release). University of Pennsylvania. Republished by ScienceDaily.
35. Huang, Xin (2021). "Dissecting dynamics and differences of selective pressures in the evolution of human pigmentation". Biology Open. 10 (2). doi:10.1242/bio.056523. PMC   7888712 . PMID   33495209.
36. Fregel, Rosa; Méndez, Fernando L.; Bokbot, Youssef; Martín-Socas, Dimas; Camalich-Massieu, María D.; Santana, Jonathan; Morales, Jacob; Ávila-Arcos, María C.; Underhill, Peter A.; Shapiro, Beth; Wojcik, Genevieve; Rasmussen, Morten; Soares, André E. R.; Kapp, Joshua; Sockell, Alexandra (26 June 2018). "Ancient genomes from North Africa evidence prehistoric migrations to the Maghreb from both the Levant and Europe". Proceedings of the National Academy of Sciences of the United States of America. 115 (26): 6774–6779. Bibcode:2018PNAS..115.6774F. doi: 10.1073/pnas.1800851115 . ISSN   1091-6490. PMC   6042094 . PMID   29895688.
37. Clements, T. L.; Adams, J. S.; Henderson, S. L.; Holick, M. F.; et al. (1982). "Increased skin pigment reduces the capacity of skin to synthesize vitamin D" (PDF). Lancet. 1 (8263): 74–76. doi:10.1016/S0140-6736(82)90214-8. PMID   6119494. S2CID   41818974.
38. Jablonski, N. G.; Chaplin, G. (2000). "The evolution of human skin coloration". Journal of Human Evolution . 39 (1): 57–106. doi:10.1006/jhev.2000.0403. PMID   10896812.
39. Webb, A. R. (2006). "Who, what, where, and when: influences on cutaneous vitamin D synthesis". Progress in Biophysics and Molecular Biology. 92 (1): 17–25. doi:10.1016/j.pbiomolbio.2006.02.004. PMID   16766240.
40. Armas, L. A.; Dowell, S.; Akhter, M.; Duthuluru, S.; Huerter, C.; Hollis, B. W.; Lund, R.; Heaney, R. P.; et al. (2007). "Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: The effect of UVB dose and skin color". Journal of the American Academy of Dermatology . 57 (4): 588–593. doi:10.1016/j.jaad.2007.03.004. PMID   17637484.
41. Chen, T. C.; et al. (2007). "Factors that influence the cutaneous synthesis and dietary sources of vitamin D". Archives of Biochemistry and Biophysics. 460 (2): 213–217. doi:10.1016/j.abb.2006.12.017. PMC   2698590 . PMID   17254541.
42. Lamason, R. L.; Mohideen, M. A.; Mest, J. R.; Wong, A. C.; Norton, H. L.; Aros, M. C.; Jurynec, M. J.; Mao, X.; Humphreville, V. R.; Humbert, J. E.; Sinha, S.; Moore, J. L.; Jagadeeswaran, P.; Zhao, W.; Ning, G.; Makalowska, I.; McKeigue, P. M.; O'Donnell, D.; Kittles, R.; Parra, E. J.; Mangini, N. J.; Grunwald, D. J.; Shriver, M. D.; Canfield, V. A.; Cheng, K. C.; et al. (2005). "SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans". Science. 310 (5755): 1782–1786. Bibcode:2005Sci...310.1782L. doi:10.1126/science.1116238. PMID   16357253. S2CID   2245002.
43. Lalueza-Fox; Römpler, H.; Caramelli, D.; Stäubert, C.; Catalano, G.; Hughes, D; Rohland, N; Pilli, E.; Longo, L.; Condemi, S.; de la Rasilla, M.; Fortea, J.; Rosas, A.; Stoneking, M.; Schöneberg, T.; Bertranpetit, J.; Hofreiter, M.; et al. (2007). "A melanocortin-1 receptor allele suggests varying pigmentation among Neanderthals". Science . 318 (5855): 1453–1455. Bibcode:2007Sci...318.1453L. doi:10.1126/science.1147417. PMID   17962522. S2CID   10087710.
44. Norton, H. L.; Kittles, R. A.; Parra, E.; McKeigue, P.; Mao, X.; Cheng, K.; Canfield, V. A.; Bradley, D. G.; McEvoy, B.; Shriver, M. D.; et al. (2007). "Genetic evidence for the convergent evolution of light skin in Europeans and East Asians". Molecular Biology and Evolution. 24 (3): 710–722. doi: 10.1093/molbev/msl203 . PMID   17182896.
45. Bergman, Ingela; Olofsson, Anders; Hörnberg, Greger; Zackrissen, Olle; Hellberg, Erik (June 2004). "Deglaciation and colonization: Pioneer settlements in northern Fennoscandia". Journal of World Prehistory. 18 (2): 155–177. doi:10.1007/s10963-004-2880-z. S2CID   129136655.
46. Bjorn, L. O.; Wang, T; et al. (2000). "Vitamin D in an ecological context". International Journal of Circumpolar Health . 59 (1): 26–32. PMID   10850004.
47. Van deer Meer; Boeke, A. J.; Lips, P.; Grootjans-Geerts, I.; Wuister, J. D.; Devillé, W. L.; Wielders, J. P.; Bouter, L. M.; Middelkoop, B. J.; et al. (2007). "Fatty fish and supplement are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population". Clinical Endocrinology. 68 (3): 466–472. doi:10.1111/j.1365-2265.2007.03066.x. hdl:1871/22170. PMID   17941903. S2CID   15728496.
48. Jablonski, Nina (2012). Living Color. Berkeley, Los Angeles, London: University of California Press. ISBN   978-0-520-25153-3.
49. Why Skin Colours Differ Department of Physics: The Faculty of Mathematics and Natural Sciences By Johan Moan, Asta Juzeniene
50. "Human Biological Adaptability: Skin Color as an Adaptation". www2.palomar.edu.
51. Post; Daniels Jr, F; Binford Jr, R. T.; et al. (1975). "Cold injury and the evolution of "white" skin". Human Biology. 47 (1): 65–80. PMID   1126703.
52. Steegman, A.T. Jr (1967). "Frostbite of the human face as a selective force". Human Biology. 39 (2): 131–144. PMID   6056270.
53. Kittles, R. (1995). "Nature, origin, and variation of human pigmentation". Journal of Black Studies. 26: 36–61. doi:10.1177/002193479502600104. S2CID   145636646.
54. Brace, C.L. (1963). "Structural reduction in evolution". American Naturalist. 97 (892): 39–49. doi:10.1086/282252. S2CID   85732039.
55. Frost, P. (1988). "Human skin color: a possible relationship between its sexual dimorphism and its social perception". Perspectives in Biology and Medicine. 32 (1): 38–59. doi:10.1353/pbm.1988.0010. PMID   3059317. S2CID   36144428.
56. Aoki, K. (2002). "Sexual selection as a cause of human skin colour variation: Darwin's hypothesis revisited". Annals of Human Biology. 29 (6): 589–608. doi:10.1080/0301446021000019144. PMID   12573076. S2CID   22703861.
57. Relethford, J.H. (1997). "Hemisphere difference in human skin color". American Journal of Physical Anthropology. 104 (4): 449–457. doi: 10.1002/(SICI)1096-8644(199712)104:4<449::AID-AJPA2>3.0.CO;2-N . PMID   9453695.
58. Chaplin, G.; Jablonski, N. (1998). "Hemisphere differences in human skin color". American Journal of Physical Anthropology. 107 (2): 221–224. doi:10.1002/(SICI)1096-8644(199810)107:2<221::AID-AJPA8>3.0.CO;2-X. PMID   9786336.
59. Miller, Craig T.; Beleza, Sandra; Pollen, Alex A.; Schluter, Dolph; Kittles, Rick A.; Shriver, Mark D.; Kingsley, David M. (2007). "cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans". Cell. 131 (6): 1179–89. doi:10.1016/j.cell.2007.10.055. PMC   2900316 . PMID   18083106.
60. HapMap: SNP report for rs642742. Hapmap.ncbi.nlm.nih.gov (19 October 2009). Retrieved on 2011-02-27.
61. "SNP report for rs2424984". International HapMap project. US National Center for Biotechnology Information. Retrieved 11 December 2012.
62. Lamason, R. L.; Mohideen, M. A.; Mest, J. R.; Wong, A. C.; Norton, H. L.; Aros, M. C.; Jurynec, M. J.; Mao, X.; et al. (2005). "SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans". Science. 310 (5755): 1782–17886. Bibcode:2005Sci...310.1782L. doi:10.1126/science.1116238. PMID   16357253. S2CID   2245002.
63. Gibbons, A. (2007). "AMERICAN ASSOCIATION OF PHYSICAL ANTHROPOLOGISTS MEETING: European Skin Turned Pale Only Recently, Gene Suggests". Science. 316 (5823): 364a. doi:10.1126/science.316.5823.364a. PMID   17446367. S2CID   43290419.
64. "Graphical display of Allele Frequencies for Ala111Thr". Allele Frequency Database. Retrieved 10 October 2012.
65. "ALFRED – Polymorphism Information – Ala111Thr". Allele Frequency Database. Retrieved 22 September 2018.
66. Pagani, Luca; Toomas Kivisild; Ayele Tarekegn; Rosemary Ekong; Chris Plaster; Irene Gallego Romero; Qasim Ayub; S. Qasim Mehdi; Mark G. Thomas; Donata Luiselli; Endashaw Bekele; Neil Bradman; David J. Balding; Chris Tyler-Smith (21 June 2012). "Ethiopian Genetic Diversity Reveals Linguistic Stratification and Complex Influences on the Ethiopian Gene Pool". American Journal of Human Genetics. 91 (1): Volume 91, Issue 1, 83–96, 21 June 2012. doi:10.1016/j.ajhg.2012.05.015. PMC   3397267 . PMID   22726845.
67. Haas et al., 2005.
68. Thong, H.Y.; et al. (2003). "The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour". British Journal of Dermatology. 149 (3): 498–505. doi:10.1046/j.1365-2133.2003.05473.x. PMID   14510981. S2CID   43355316.
69. Wondrak, Georg (2016), Skin Stress Response Pathways: Environmental Factors and Molecular Opportunities, Springer International Publishing, p. 159, ISBN   9783319431574 , retrieved 6 April 2020
70. Szabo, G.; et al. (1969). "Racial differences in the fate of melanosomes in human epidermis". Nature. 222 (5198): 1081–1082. Bibcode:1969Natur.222.1081S. doi:10.1038/2221081a0. PMID   5787098. S2CID   4223552.
71. Jablonski, N.G. (2006). Skin: a Natural History. Berkeley, CA: University of California Press.
72. Sturm, R.A.; et al. (2003). "Genetic association and cellular function of MC1R variant alleles in human pigmentation". Annals of the New York Academy of Sciences. 994 (1): 348–358. Bibcode:2003NYASA.994..348S. doi:10.1111/j.1749-6632.2003.tb03199.x. PMID   12851335. S2CID   6156245.
73. Rees, J.L. (2003). "Genetics of hair and skin color". Annual Review of Genetics. 37: 67–90. doi:10.1146/annurev.genet.37.110801.143233. PMID   14616056.
74. Alaluf, S.; et al. (2002). "Ethnic variation in melanin content and composition in photo exposed and photo protected human sjin". Pigment Cell Research. 15 (2): 112–118. doi:10.1034/j.1600-0749.2002.1o071.x. PMID   11936268.
75. Minwala, S.; et al. (2001). "Keratinocytes Play a Role in Regulating Distribution Patterns of Recipient Melanosomes in Vitro". Journal of Investigative Dermatology. 117 (2): 341–347. doi: 10.1046/j.0022-202x.2001.01411.x . PMID   11511313.
76. Rhodes, A. R.; et al. (1991). "Sun-induced freckles in children and young adults: a correlation of clinical and histopathologic features". Cancer . 67 (7): 1990–2001. doi: 10.1002/1097-0142(19910401)67:7<1990::aid-cncr2820670728>3.0.co;2-p . PMID   2004316.
77. Fitzpatrick, T. B.; Ortonne, J. P. (2003). "Normal skin color and general considerations of pigmentary disorders". In Fitzpatrick's Dermatology in General Medicine. 6: 819–825.
78. Cleaver, J. E.; Crowely, E. (2002). "UV damage, DNA repair and skin carcinogenesis". Frontiers in Bioscience. 7 (1–3): 1024–1043. doi: 10.2741/cleaver . PMID   11897551.
79. Matsumura, Yasuhiro; Ananthawamy, Honnavara N. (2004). "Toxic effects of ultraviolet radiation in the skin". Toxicology and Applied Pharmacology . 195 (3): 298–308. doi:10.1016/j.taap.2003.08.019. PMID   15020192.
80. Tadokoro, T.; et al. (2005). "Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation". Journal of Investigative Dermatology. 124 (6): 1326–1332. doi: 10.1111/j.0022-202X.2005.23760.x . PMID   15955111.
81. Nielsen, K.P.; et al. (2006a). "The importance of the depth distribution of melanin in skin for DNA protection and other photobiological processes". Journal of Photochemistry and Photobiology B: Biology. 82 (3): 194–198. doi:10.1016/j.jphotobiol.2005.11.008. PMID   16388960.
82. Cui, Xiaoying; McGrath, John J.; Burne, Thomas H. J.; Eyles, Darryl W. (26 January 2021). "Vitamin D and schizophrenia: 20 years on". Nature. 26 (7): 2708–2720. doi:10.1038/s41380-021-01025-0. PMC   8505257 . PMID   33500553. A separate observation that the offspring of migrants with dark skin who migrate to cold climates have an increased risk of schizophrenia may also be due to low vitamin D during gestation and early life as dark skin requires greater sunlight exposure to make adequate levels of the vitamin D prehormone.
83. Djukic, A. (2007). "Folate-resposive neurologic diseases". Pediatric Neurology . 37 (6): 387–397. doi:10.1016/j.pediatrneurol.2007.09.001. PMID   18021918.
84. Norton, Amy (10 November 2010). "White women's skin may show wrinkles sooner". Reuters . Retrieved 22 September 2018.
85. Cole, Gary. "Wrinkles". MedicineNet.com. Retrieved 22 September 2018.