Editing Human skin color (section)

==== Europe ====
A number of genes have been positively associated with the skin pigmentation difference between European and non-European populations. Mutations in SLC24A5 and SLC45A2 are believed to account for the bulk of this variation and show very strong signs of selection. A variation in TYR has also been identified as a contributor.

Research indicates the selection for the light-skin alleles of these genes in Europeans is comparatively recent, having occurred later than 20,000 years ago and perhaps as recently as 12,000 to 6,000 years ago.<ref name=Belezal2012 /> In the 1970s, [[Luca Cavalli-Sforza]] suggested that the selective sweep that rendered light skin ubiquitous in Europe might be correlated with the [[Neolithic Revolution|advent of farming]] and thus have taken place only around 6,000 years ago;<ref name="pmid17446367">{{cite journal |last1=Gibbons |first1=A. |doi=10.1126/science.316.5823.364a |title=European Skin Turned Pale Only Recently, Gene Suggests |year=2007 |pages=364a |volume=316 |journal=Science |issue=5823|pmid=17446367|s2cid=43290419 |url=http://galsatia.files.wordpress.com/2007/04/blanche_paleur.pdf |archive-url= https://web.archive.org/web/20101103171424/http://galsatia.files.wordpress.com//2007//04//blanche_paleur.pdf |archive-date=2010-11-03 |url-status=dead |access-date=2011-01-26}} "a suggestion made 30 years ago by Stanford University geneticist L. Luca Cavalli-Sforza … that the early immigrants to Europe … survived on ready-made sources of vitamin D in their diet. But when farming spread in the past 6,000 years, he argued, Europeans had fewer sources of vitamin D in their food and needed to absorb more sunlight to produce the vitamin in their skin."</ref> This scenario found support in a 2014 analysis of [[Mesolithic]] (7,000 years old) [[hunter-gatherer]] DNA from [[La Braña]], Spain, which showed a version of these genes not corresponding with light skin color.<ref>{{cite journal |title= Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European|journal=Nature|volume=507|issue=7491|pages=225–228 |doi=10.1038/nature12960|pmid=24463515|quote=The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic time|year=2014|last1=Olalde|first1=Iñigo|last2=Allentoft|first2=Morten E.|last3=Sánchez-Quinto |first3=Federico|last4=Santpere|first4=Gabriel|last5=Chiang|first5=Charleston W. K.|last6=Degiorgio |first6=Michael|last7=Prado-Martinez|first7=Javier|last8=Rodríguez|first8=Juan Antonio|last9=Rasmussen |first9=Simon|last10=Quilez |first10=Javier|last11=Ramírez|first11=Oscar|last12=Marigorta|first12=Urko M. |last13=Fernández-Callejo|first13=Marcos|last14=Prada|first14=María Encina|last15=Encinas|first15=Julio Manuel Vidal|last16=Nielsen|first16=Rasmus |last17=Netea|first17=Mihai G.|last18=Novembre|first18=John |last19=Sturm|first19=Richard A.|last20=Sabeti|first20=Pardis|author20-link=Pardis Sabeti|last21=Marquès-Bonet|first21=Tomàs |last22=Navarro|first22=Arcadi|last23=Willerslev|first23=Eske |last24=Lalueza-Fox|first24=Carles |pmc=4269527|bibcode=2014Natur.507..225O}}</ref> 

In 2015, researchers analysed for light skin genes in the DNA of 94 ancient skeletons ranging from 8,000 to 3,000 years old from Europe and Russia. They found c. 8,000-year-old hunter-gatherers in Spain, Luxembourg, and Hungary were dark skinned while similarly aged hunter gatherers in Sweden were light skinned (having predominately derived alleles of SLC24A5, SLC45A2 and also HERC2/OCA2). [[Early European Farmers|Neolithic farmers]] entering Europe at around the same time were intermediate, being nearly fixed for the derived SLC24A5 variant but only having the derived SLC45A2 allele in low frequencies. The SLC24A5 variant spread very rapidly throughout central and southern Europe from about 8,000 years ago, whereas the light skin variant of SLC45A2 spread throughout Europe after 5,800 years ago.<ref>{{cite journal |last=Gibbons |first=Ann |date=2 April 2015 |url=https://www.science.org/content/article/how-europeans-evolved-white-skin |title=How Europeans evolved white skin |doi=10.1126/science.aab2435 |archive-url=https://web.archive.org/web/20150414000323/http://news.sciencemag.org/archaeology/2015/04/how-europeans-evolved-white-skin |archive-date=2015-04-14 |journal=Science |access-date=13 April 2015 |url-status=live}}</ref><ref>{{cite bioRxiv |biorxiv=10.1101/016477|title=Eight thousand years of natural selection in Europe|year=2015 |last1=Mathieson |first1=I. |last2=Lazaridis |first2=I. |last3=Rohland |first3=N. |last4=Mallick |first4=S. |last5=Llamas |first5=B. |last6=Pickrell |first6=J. |last7=Meller |first7=H. |last8=Rojo Guerra |first8=M. A. |last9=Krause |first9=J. |last10=Anthony |first10=D. |last11=Brown |first11=D. |last12=Lalueza Fox |first12=C. |last13=Cooper |first13=A. |last14=Alt |first14=K. W. |last15=Haak |first15=W. |last16=Patterson |first16=N. |last17=Reich |first17=D.}}</ref>

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, stated:<blockquote>"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."<ref>{{cite journal |journal=PNAS |volume=118 |issue=1 |date=2021 |title=The evolution of skin pigmentation-associated variation in West Eurasia |last1=Ju |first1=Dan |last2=Mathieson |first2=Ian|pages=e2009227118 |doi=10.1073/pnas.2009227118|pmid=33443182 |pmc=7817156 |bibcode=2021PNAS..11809227J |quote="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." |doi-access=free }}</ref></blockquote>

===== SLC24A5 =====
[[SLC24A5|Solute carrier family 24 member 5]] (SLC24A5) regulates calcium in melanocytes and is important in the process of melanogenesis.<ref name="pmid18166528">{{cite journal |last1=Ginger |first1=R. S. |last2=Askew |first2=S. E. |last3=Ogborne |first3=R. M. |last4=Wilson |first4=S. |last5=Ferdinando |first5=D. |last6=Dadd |first6=T. |last7=Smith |first7=A. M. |last8=Kazi |first8=S. |last9=Szerencsei |first9=R. T. |last10=Winkfein |first10=R. J. |last11=Schnetkamp |first11=P. P. M. |last12=Green |first12=M. R. |title=SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis |journal=Journal of Biological Chemistry |volume=283 |issue=9 |pages=5486–95 |year=2007 |pmid=18166528 |doi=10.1074/jbc.M707521200|doi-access=free }}</ref> The SLC24A5 gene's derived ''Ala111Thr'' allele (rs1426654<ref name="ncbi_rs14">{{Cite web |title=rs1426654 RefSNP Report |author= |work=ncbi.nlm.nih.gov |date= |access-date=15 February 2021 |url= https://www.ncbi.nlm.nih.gov/snp/rs1426654 |quote=}}</ref>) has been shown to be a major factor in light skin pigmentation and is common in Western [[Eurasia]].<ref name=Valenzuela /> Recent studies have found that the variant represents as much as 25–40% of the average skin tone difference between Europeans and West Africans.<ref name=Norton2006 /><ref name="pmid16357253">{{cite journal |last1=Lamason |first1=R. L. |last2=Mohideen |first2=MA |last3=Mest |first3=JR |last4=Wong |first4=AC |last5=Norton |first5=HL |last6=Aros |first6=MC |last7=Jurynec |first7=MJ |last8=Mao |first8=X |last9=Humphreville |first9=VR |last10=Humbert |first10=J. E. |last11=Sinha |first11=S |last12=Moore |first12=J. L. |last13=Jagadeeswaran |first13=P |last14=Zhao |first14=W |last15=Ning |first15=G |last16=Makalowska |first16=I |last17=McKeigue |first17=P. M. |last18=O'Donnell |first18=D |last19=Kittles |first19=R |last20=Parra |first20=E. J. |last21=Mangini |first21=N. J. |last22=Grunwald |first22=D. J. |last23=Shriver |first23=M. D. |last24=Canfield |first24=V. A. |last25=Cheng |first25=K. C. |title=SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans |journal=Science |volume=310 |issue=5755 |pages=1782–6 |year=2005 |pmid=16357253 |doi=10.1126/science.1116238 |bibcode=2005Sci...310.1782L |s2cid=2245002}}</ref> This derived allele is a reliable predictor of phenotype across a range of populations.<ref name=Lopez>{{cite journal |last1=López |first1=Saioa |title=The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population |journal=PLOS ONE |volume=9 |issue=8 |pages=e104367 |date=5 August 2014 |doi=10.1371/journal.pone.0104367 |pmid=25093503 |pmc=4122405 |bibcode=2014PLoSO...9j4367L |doi-access=free }}</ref><ref name=Stokowski2007 /> It has been the subject of recent selection in Western Eurasia, and is fixed in European populations.<ref name=Belezal2012 /><ref name=Soejima2006>{{cite journal |last1=Soejima |first1=Mikiko |last2=Koda |first2=Yoshiro |title=Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2 |journal=International Journal of Legal Medicine |volume=121 |issue=1 |pages=36–9 |year=2006 |pmid=16847698 |doi=10.1007/s00414-006-0112-z|s2cid=11192076 }}</ref><ref name=Khai2012>{{cite journal |title=Skin Color Variation in Orang Asli Tribes of Peninsular Malaysia |journal=PLOS ONE |volume=7 |issue=8 |pages=e42752 |doi=10.1371/journal.pone.0042752 |year=2012 |pmid=22912732 |pmc=3418284 |bibcode=2012PLoSO...742752A |last1=Ang |first1=K. C. |last2=Ngu |first2=M. S. |last3=Reid |first3=K. P. |last4=Teh |first4=M. S. |last5=Aida |first5=Z. S. |last6=Koh |first6=D. X. |last7=Berg |first7=A |last8=Oppenheimer |first8=S |last9=Salleh |first9=H |last10=Clyde |first10=M. M. |last11=Md-Zain |first11=B. M. |last12=Canfield |first12=V. A. |last13=Cheng |first13=K. C. |doi-access=free }}</ref>

===== SLC45A2 =====
[[SLC45A2|Solute carrier family 45 member 2]] (SLC45A2 or MATP) aids in the transport and processing of tyrosine, a precursor to melanin. It has also been shown to be one of the significant components of the skin color of modern Europeans through its ''Phe374Leu'' ([[rs16891982]]<ref>{{Cite web |title=rs16891982 RefSNP Report - dbSNP - NCBI |url=https://www.ncbi.nlm.nih.gov/snp/rs16891982 |access-date=2022-10-02 |website=www.ncbi.nlm.nih.gov}}</ref>) allele that has been directly correlated with skin color variation across a range of populations.<ref>{{cite journal |last1=Adhikari |first1=Kaustubh |title=A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia |journal=Nature Communications |volume=10 |issue=1 |pages=358 |date=21 January 2019 |doi=10.1038/s41467-018-08147-0 |pmid=30664655 |pmc=6341102 |bibcode=2019NatCo..10..358A }}</ref><ref>{{cite journal |last1=Deng |first1=Lian |title=Adaptation of human skin color in various populations |journal=Hereditas |volume=155 |pages=1 |date=15 June 2017 |doi=10.1186/s41065-017-0036-2 |pmid=28701907 |pmc=5502412 |doi-access=free }}</ref><ref name=Lopez/><ref name=Valenzuela /><ref name=Stokowski2007 /> This variation is ubiquitous in European populations but extremely rare elsewhere and shows strong signs of selection.<ref name=Soejima2006 /><ref name=Khai2012 /><ref>{{cite journal |title=Evidence for Recent Positive Selection at the Human AIM1 Locus in a European Population |journal=Molecular Biology and Evolution |date=January 2006 |volume=23 |issue=1 |pages=179–188 |doi=10.1093/molbev/msj018 |pmid=16162863 |last1=Soejima |first1=M |last2=Tachida |first2=H |last3=Ishida |first3=T |last4=Sano |first4=A |last5=Koda |first5=Y }}</ref>

===== TYR =====
The [[TYR gene]] encodes the enzyme tyrosinase, which is involved in the production of melanin from tyrosine. It has an allele, ''Ser192Tyr'' (rs1042602<ref>[https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1042602 Reference SNP(refSNP) Cluster Report: rs1042602 **clinically associated**] {{webarchive|url= https://web.archive.org/web/20160416220943/http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1042602 |date=2016-04-16 }}. Ncbi.nlm.nih.gov (2008-12-30). Retrieved 2011-02-27.</ref>), found solely in 40–50% of Europeans<ref name="Norton2006" /><ref name=Belezal2012 /> and linked to light-colored skin in studies of South Asian<ref name=Stokowski2007>{{cite journal |last1=Stokowski |first1=R |last2=Pant |first2=P |last3=Dadd |first3=T |last4=Fereday |first4=A |last5=Hinds |first5=D |last6=Jarman |first6=C |last7=Filsell |first7=W |last8=Ginger |first8=R |last9=Green |first9=M |last10=Van Der Ouderaa |first10=Frans J. |last11=Cox |first11=David R. |title=A Genomewide Association Study of Skin Pigmentation in a South Asian Population |journal=The American Journal of Human Genetics |volume=81 |pages=1119–32 |year=2007 |doi=10.1086/522235 |pmid=17999355 |issue=6 |pmc=2276347 }}</ref> and African-American<ref name=Shriver2003>{{cite journal|url=http://dl.dropbox.com/u/38568440/admixture/shriver01.pdf |title=Skin pigmentation, biogeographical ancestry and admixture mapping |journal=Human Genetics |year=2003 |volume=112 |issue=4 |pages=387–399 |doi=10.1007/s00439-002-0896-y |pmid=12579416 |last1=Shriver|first1=MD |last2=Parra|first2=EJ |last3=Dios|first3=S |last4=Bonilla |first4=C |last5=Norton|first5=H |last6=Jovel|first6=C |last7=Pfaff |first7=C |last8=Jones|first8=C |last9=Massac|first9=A |last10=Cameron|first10=N |last11=Baron|first11=A |last12=Jackson|first12=T |last13=Argyropoulos|first13=G |last14=Jin|first14=L |last15=Hoggart|first15=CJ |last16=McKeigue|first16=PM |last17=Kittles|first17=RA |s2cid=7877572 |url-status=dead |archive-url= https://web.archive.org/web/20120415112141/http://dl.dropbox.com/u/38568440/admixture/shriver01.pdf |archive-date=2012-04-15}}</ref> populations.