Ectodysplasin A receptor
Ectodysplasin A receptor (EDAR) is a
Function
EDAR and other genes provide instructions for making proteins that work together during
Clinical significance
Mutation in this gene have been associated with
Derived EDAR allele
A derived G-allele point mutation (
A 2013 study suggested that the EDAR variant (370A) arose about 35,000 years ago in central China, period during which the region was then quite warm and humid.[7] A subsequent study from 2021, based on ancient DNA samples, has suggested that the derived variant became dominant among "Ancient Northern East Asians" shortly after the Last Glacial Maximum in Northeast Asia, around 19,000 years ago. Ancient remains from Northern East Asia, such as the Tianyuan Man (40,000 years old) and the AR33K (33,000 years old) specimen lacked the derived EDAR allele, while ancient East Asian remains after the LGM carry the derived EDAR allele.[8][9] The frequency of 370A is most highly elevated in North Asian and East Asian populations.[10] In a study of 222 Korean and 265 Japanese subjects, the 370A mutation was found in 86.9% Korean (Busan) and 77.5% Japanese (Tokyo) subjects.[11] This mutation is also implicated in ear morphology differences and reduced chin protrusion.[12]
It has been hypothesized that natural selection favored this allele during the last ice age in a population of people living in isolation in Beringia, as it may play a role in the synthesis of Vitamin D-rich breast milk in dark environments.[13][14][15] One study suggested that because the EDAR mutation arose in a cool and dry environment, it may have been adaptive by increasing skin lubrication, thus reducing dryness in exposed facial structures.[16]
The derived G-allele is a variation of the A-allele in earlier hominids, the version found in most modern non-East Asian and non-Native American populations and is found in 100% of Native American skeletal remains within all Native American haplogroups which studies have been done on prior to all contract for foreign population from Africa, Europe, or Asia. The derived allele was present in both the Tibeto-Burman (Magar and Newar) and Indo-European (Brahmin) populations of Nepal. The highest 1540C allele frequency was observed in Magar (71%), followed by Newar (30%) and Brahmin (20%).[5]
Derived variants of EDAR are associated with multiple facial and dental characteristics.[17][18]
50% of ancient DNA samples (7,900-7,500 BP) from
According to a 2018 study, several ancient DNA samples from the Americas, including USR1 from the Upward Sun River site, Anzick-1, and the 9,600 BP individual from Lapa do Santo, were found to not carry the derived allele. This suggests that the increased frequency of the derived allele occurred independently in both East Asia and the Americas.[20]
A 2021 study analyzed the DNA of 6
See also
References
- S2CID 11348633.
- PMID 9375732.
- ^ a b c "Entrez Gene: EDAR ectodysplasin A receptor".
- ^ Online Mendelian Inheritance in Man (OMIM): 604095
- ^ S2CID 252904281.
- PMID 23415220.
- ^ "EDAR gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-10-18.
- PMID 34048699.
- S2CID 250502011.
- PMID 29686092.
- ISSN 1435-232X.
- PMID 27193062.
- ^ Lozovschi, Alexandra (24 April 2018). "Ancient Teeth Reveal Breastfeeding-Related Gene Helped Early Americans Survive The Ice Age [Study]". Inquisitr. Retrieved 25 April 2018.
- ^ Nicholas Wade (February 14, 2013). "East Asian Physical Traits Linked to 35,000-Year-Old Mutation". The New York Times. Retrieved February 15, 2013.
- PMID 29686092.
- PMID 19855838. "As this allele attained high frequency in an environment that was notably cold and dry, increased glandular secretions could represent a trait that was positively selected to achieve increased lubrication and reduced evaporation from exposed facial structures and upper airways"
- PMID 27193062.
- PMID 33618348.
- PMID 26595274.
- PMID 30415837.
- PMC 7993749. "None of our reported 6 Jomon individuals carries the derived allele at the EDARV370A variant in the human Ectodysplasin receptor which affects hair, sweat, and mammary glands (Online Table 15), which has been estimated to have arisen in mainland China ~30,000 years ago24 and then swept to high frequency in nearly all Holocene people from mainland East Asia and the Americas."
Further reading
- Thesleff I, Mikkola ML (May 2002). "Death receptor signaling giving life to ectodermal organs". Science's STKE. 2002 (131): pe22. S2CID 36068881.
- Ho L, Williams MS, Spritz RA (May 1998). "A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11-q13". American Journal of Human Genetics. 62 (5): 1102–6. PMID 9545409.
- Kumar A, Eby MT, Sinha S, Jasmin A, Chaudhary PM (January 2001). "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A". The Journal of Biological Chemistry. 276 (4): 2668–77. PMID 11035039.
- Yan M, Wang LC, Hymowitz SG, Schilbach S, Lee J, Goddard A, et al. (October 2000). "Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors". Science. 290 (5491): 523–7. PMID 11039935.
- Elomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J (April 2001). "Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein". Human Molecular Genetics. 10 (9): 953–62. PMID 11309369.
- Koppinen P, Pispa J, Laurikkala J, Thesleff I, Mikkola ML (October 2001). "Signaling and subcellular localization of the TNF receptor Edar". Experimental Cell Research. 269 (2): 180–92. PMID 11570810.
- Headon DJ, Emmal SA, Ferguson BM, Tucker AS, Justice MJ, Sharpe PT, et al. (2002). "Gene defect in ectodermal dysplasia implicates a death domain adapter in development". Nature. 414 (6866): 913–6. S2CID 4380080.
- Yan M, Zhang Z, Brady JR, Schilbach S, Fairbrother WJ, Dixit VM (March 2002). "Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice". Current Biology. 12 (5): 409–13. S2CID 9911697.
- Sinha SK, Zachariah S, Quiñones HI, Shindo M, Chaudhary PM (November 2002). "Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor". The Journal of Biological Chemistry. 277 (47): 44953–61. PMID 12270937.
- Shu H, Chen S, Bi Q, Mumby M, Brekken DL (March 2004). "Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line". Molecular & Cellular Proteomics. 3 (3): 279–86. PMID 14729942.
- Zhang Z, Henzel WJ (October 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. PMID 15340161.
- Hashimoto T, Cui CY, Schlessinger D (April 2006). "Repertoire of mouse ectodysplasin-A (EDA-A) isoforms". Gene. 371 (1): 42–51. PMID 16423472.
- Chassaing N, Bourthoumieu S, Cossee M, Calvas P, Vincent MC (March 2006). "Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia". Human Mutation. 27 (3): 255–9. S2CID 32110651.
- Tariq M, Wasif N, Ahmad W (July 2007). "A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia". The British Journal of Dermatology. 157 (1): 207–9. S2CID 310090.