Ectodysplasin A receptor

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Ectodysplasin A receptor (EDAR) is a protein that in humans is encoded by the EDAR gene. EDAR is a cell surface receptor for ectodysplasin A which plays an important role in the development of ectodermal tissues such as the skin. [1] [2] [3] It is structurally related to members of the TNF receptor superfamily. [4]

Contents

Function

EDAR and other genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the proper formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands. [3]

Clinical significance

Mutation in this gene have been associated with hypohidrotic ectodermal dysplasia, a disorder characterized by a lower density of sweat glands. [3]

Derived EDAR allele

A derived G-allele point mutation (SNP) with pleiotropic effects in EDAR, 370A or rs3827760, found in ancient and modern East Asians, Southeast Asians, Nepalese [5] and Native Americans but not common in African or European populations. Experimental research in mice has linked the derived allele to a number of traits, including greater hair shaft diameter, more numerous sweat glands, smaller mammary fat pad, and increased mammary gland density. [6]

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 Motala, Sweden; two (3300–3000 BC) from the Afanasevo culture and one (400–200 BC) Scythian sample were found to carry the rs3827760 mutation. [19]

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 Jomon remains from Japan and found that none of them carried the derived EDAR allele that is fixed in modern East Asian populations. [21]

See also

Related Research Articles

<span class="mw-page-title-main">Ectoderm</span> Outer germ layer of embryonic development

The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm and endoderm. It emerges and originates from the outer layer of germ cells. The word ectoderm comes from the Greek ektos meaning "outside", and derma meaning "skin".

Black hair is the darkest and most common of all human hair colors globally, due to large populations with this trait. This hair type contains a much more dense quantity of eumelanin pigmentation in comparison to other hair colors, such as brown, blonde and red. In English, various types of black hair are sometimes described as soft-black, raven black, or jet-black. The range of skin colors associated with black hair is vast, ranging from the palest of light skin tones to dark skin. Black-haired humans can have dark or light eyes.

<span class="mw-page-title-main">Ectrodactyly–ectodermal dysplasia–cleft syndrome</span> Medical condition

Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome and split hand–split foot–ectodermal dysplasia–cleft syndrome is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.

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<span class="mw-page-title-main">Hypohidrotic ectodermal dysplasia</span> Medical condition

Hypohidrotic ectodermal dysplasia is one of about 150 types of ectodermal dysplasia in humans. Before birth, these disorders result in the abnormal development of structures including the skin, hair, nails, teeth, and sweat glands.

<span class="mw-page-title-main">Shovel-shaped incisors</span> Possible shape of human incisor teeth

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<span class="mw-page-title-main">Hay–Wells syndrome</span> Medical condition

Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.

<span class="mw-page-title-main">Laminopathy</span> Medical condition

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<span class="mw-page-title-main">IKBKG</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Rosselli–Gulienetti syndrome</span> Medical condition

Rosselli–Gulienetti syndrome, also known as Zlotogora–Ogur syndrome and Bowen–Armstrong syndrome, is a type of congenital ectodermal dysplasia syndrome. The syndrome is relatively rare and has only been described in a few cases.

<span class="mw-page-title-main">Sulfate transporter</span> Protein-coding gene in the species Homo sapiens

The sulfate transporter is a solute carrier family protein that in humans is encoded by the SLC26A2 gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A defect in sulfate activation described by Superti-Furga in achondrogenesis type 1B was subsequently also found to be caused by genetic variants in the sulfate transporter gene. This sulfate (SO42−) transporter also accepts chloride, hydroxyl ions (OH−), and oxalate as substrates. SLC26A2 is expressed at high levels in developing and mature cartilage, as well as being expressed in lung, placenta, colon, kidney, pancreas and testis.

<span class="mw-page-title-main">TP63</span> Protein-coding gene in the species Homo sapiens

Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.

<span class="mw-page-title-main">Ectodysplasin A</span> Protein-coding gene in humans

Ectodysplasin A (EDA) is a protein that in humans is encoded by the EDA gene.

<span class="mw-page-title-main">TNFRSF19</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily, member 19, also known as TNFRSF19 and TROY is a human gene.

<span class="mw-page-title-main">EDARADD</span> Protein-coding gene in the species Homo sapiens

Ectodysplasin-A receptor-associated adapter protein is a protein that in humans is encoded by the EDARADD gene.

<span class="mw-page-title-main">Ectodysplasin A2 receptor</span> Protein-coding gene in humans

Tumor necrosis factor receptor superfamily member 27 is a protein that in humans is encoded by the EDA2R gene.

TOX high mobility group box family member 3, also known as TOX3, is a human gene.

<span class="mw-page-title-main">Melanocortin 1 receptor</span> Protein controlling mammalian coloration

The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones known as the melanocortins, which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH). It is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase in cells expressing this receptor. It is normally expressed in skin and melanocytes, and to a lesser degree in periaqueductal gray matter, astrocytes and leukocytes. In skin cancer, MC1R is highly expressed in melanomas but not carcinomas.

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<span class="mw-page-title-main">Hypohidrotic ectodermal dysplasia with immune deficiency</span> Medical condition

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References

  1. ↑ Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J (August 1999). "Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia". Nature Genetics. 22 (4): 366–9. doi:10.1038/11937. PMID   10431241. S2CID   11348633.
  2. ↑ Aswegan AL, Josephson KD, Mowbray R, Pauli RM, Spritz RA, Williams MS (November 1997). "Autosomal dominant hypohidrotic ectodermal dysplasia in a large family". American Journal of Medical Genetics. 72 (4): 462–7. doi:10.1002/(SICI)1096-8628(19971112)72:4<462::AID-AJMG17>3.0.CO;2-P. PMID   9375732.
  3. 1 2 3 "Entrez Gene: EDAR ectodysplasin A receptor".
  4. ↑ Online Mendelian Inheritance in Man (OMIM): 604095
  5. 1 2 Basnet, Rajdip; Rai, Niraj; Tamang, Rakesh; Awasthi, Nagendra Prasad; Pradhan, Isha; Parajuli, Pawan; Kashyap, Deepak; Reddy, Alla Govardhan; Chaubey, Gyaneshwer; Das Manandhar, Krishna; Shrestha, Tilak Ram; Thangaraj, Kumarasamy (2022-10-15). "The matrilineal ancestry of Nepali populations". Human Genetics. 142 (2): 167–180. doi:10.1007/s00439-022-02488-z. ISSN   0340-6717. PMID   36242641. S2CID   252904281.
  6. ↑ Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, et al. (February 2013). "Modeling recent human evolution in mice by expression of a selected EDAR variant". Cell. 152 (4): 691–702. doi:10.1016/j.cell.2013.01.016. PMC   3575602 . PMID   23415220.
  7. ↑ "EDAR gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-10-18.
  8. ↑ Mao, Xiaowei; Zhang, Hucai; Qiao, Shiyu; Liu, Yichen; Chang, Fengqin; Xie, Ping; Zhang, Ming; Wang, Tianyi; Li, Mian; Cao, Peng; Yang, Ruowei; Liu, Feng; Dai, Qingyan; Feng, Xiaotian; Ping, Wanjing (2021-06-10). "The deep population history of northern East Asia from the Late Pleistocene to the Holocene". Cell. 184 (12): 3256–3266.e13. doi: 10.1016/j.cell.2021.04.040 . ISSN   0092-8674. PMID   34048699.
  9. ↑ Zhang, Xiaoming; Ji, Xueping; Li, Chunmei; Yang, Tingyu; Huang, Jiahui; Zhao, Yinhui; Wu, Yun; Ma, Shiwu; Pang, Yuhong; Huang, Yanyi; He, Yaoxi; Su, Bing (25 July 2022). "A Late Pleistocene human genome from Southwest China". Current Biology. 32 (14): 3095–3109.e5. Bibcode:2022CBio...32E3095Z. doi: 10.1016/j.cub.2022.06.016 . ISSN   0960-9822. PMID   35839766. S2CID   250502011.
  10. ↑ Hlusko, Leslea J.; Carlson, Joshua P.; Chaplin, George; Elias, Scott A.; Hoffecker, John F.; Huffman, Michaela; Jablonski, Nina G.; Monson, Tesla A.; O’Rourke, Dennis H.; Pilloud, Marin A.; Scott, G. Richard (2018-05-08). "Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk". Proceedings of the National Academy of Sciences. 115 (19): E4426–E4432. Bibcode:2018PNAS..115E4426H. doi: 10.1073/pnas.1711788115 . ISSN   0027-8424. PMC   5948952 . PMID   29686092.
  11. ↑ Park, Jeong-Heuy; Yamaguchi, Tetsutaro; Watanabe, Chiaki; Kawaguchi, Akira; Haneji, Kuniaki; Takeda, Mayako; Kim, Yong-Il; Tomoyasu, Yoko; Watanabe, Miyuki; Oota, Hiroki; Hanihara, Tsunehiko; Ishida, Hajime; Maki, Koutaro; Park, Soo-Byung; Kimura, Ryosuke (August 2012). "Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits". Journal of Human Genetics. 57 (8): 508–514. doi: 10.1038/jhg.2012.60 . ISSN   1435-232X. PMID   22648185.
  12. ↑ Adhikari K, Fuentes-Guajardo M, Quinto-Sánchez M, Mendoza-Revilla J, Camilo Chacón-Duque J, Acuña-Alonzo V, et al. (May 2016). "A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation". Nature Communications. 7: 11616. Bibcode:2016NatCo...711616A. doi:10.1038/ncomms11616. PMC   4874031 . PMID   27193062.
  13. ↑ Lozovschi, Alexandra (24 April 2018). "Ancient Teeth Reveal Breastfeeding-Related Gene Helped Early Americans Survive The Ice Age [Study]". Inquisitr. Retrieved 25 April 2018.
  14. ↑ Nicholas Wade (February 14, 2013). "East Asian Physical Traits Linked to 35,000-Year-Old Mutation". The New York Times. Retrieved February 15, 2013.
  15. ↑ Hlusko LJ, Carlson JP, Chaplin G, Elias SA, Hoffecker JF, Huffman M, et al. (May 2018). "Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk". Proceedings of the National Academy of Sciences of the United States of America. 115 (19): E4426–E4432. Bibcode:2018PNAS..115E4426H. doi: 10.1073/pnas.1711788115 . PMC   5948952 . PMID   29686092.
  16. ↑ Chang, Shie Hong; Jobling, Stephanie; Brennan, Keith; Headon, Denis J. (26 October 2009). "Enhanced Edar Signalling Has Pleiotropic Effects on Craniofacial and Cutaneous Glands". PLOS ONE. 4 (10): e7591. Bibcode:2009PLoSO...4.7591C. doi: 10.1371/journal.pone.0007591 . ISSN   1932-6203. PMC   2762540 . 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"
  17. ↑ Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez; Mendoza-Revilla; Camilo Chacón-Duque (2016). "A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation". Nature Communications. 7 (1): 11616. Bibcode:2016NatCo...711616A. doi:10.1038/ncomms11616. ISSN   2041-1723. PMC   4874031 . PMID   27193062.
  18. ↑ Wang, Chuan-Chao; Yeh, Hui-Yuan; Popov, Alexander N.; Zhang, Hu-Qin; Matsumura, Hirofumi; Sirak, Kendra; Cheronet, Olivia; Kovalev, Alexey; Rohland, Nadin; Kim, Alexander M.; Mallick, Swapan; Bernardos, Rebecca; Tumen, Dashtseveg; Zhao, Jing; Liu, Yi-Chang; Liu, Jiun-Yu; Mah, Matthew; Wang, Ke; Zhang, Zhao; Adamski, Nicole; Broomandkhoshbacht, Nasreen; Callan, Kimberly; Candilio, Francesca; Carlson, Kellie Sara Duffett; Culleton, Brendan J.; Eccles, Laurie; Freilich, Suzanne; Keating, Denise; Lawson, Ann Marie; Mandl, Kirsten; Michel, Megan; Oppenheimer, Jonas; Özdoğan, Kadir Toykan; Stewardson, Kristin; Wen, Shaoqing; Yan, Shi; Zalzala, Fatma; Chuang, Richard; Huang, Ching-Jung; Looh, Hana; Shiung, Chung-Ching; Nikitin, Yuri G.; Tabarev, Andrei V.; Tishkin, Alexey A.; Lin, Song; Sun, Zhou-Yong; Wu, Xiao-Ming; Yang, Tie-Lin; Hu, Xi; Chen, Liang; Du, Hua; Bayarsaikhan, Jamsranjav; Mijiddorj, Enkhbayar; Erdenebaatar, Diimaajav; Iderkhangai, Tumur-Ochir; Myagmar, Erdene; Kanzawa-Kiriyama, Hideaki; Nishino, Masato; Shinoda, Ken-ichi; Shubina, Olga A.; Guo, Jianxin; Cai, Wangwei; Deng, Qiongying; Kang, Longli; Li, Dawei; Li, Dongna; Lin, Rong; Shrestha, Rukesh; Wang, Ling-Xiang; Wei, Lanhai; Xie, Guangmao; Yao, Hongbing; Zhang, Manfei; He, Guanglin; Yang, Xiaomin; Hu, Rong; Robbeets, Martine; Schiffels, Stephan; Kennett, Douglas J.; Jin, Li; Li, Hui; Krause, Johannes; Pinhasi, Ron; Reich, David (March 2021). "Genomic insights into the formation of human populations in East Asia". Nature. 591 (7850): 413–419. Bibcode:2021Natur.591..413W. doi:10.1038/s41586-021-03336-2. ISSN   1476-4687. PMC   7993749 . PMID   33618348.
  19. ↑ Mathieson I, Lazaridis I, Rohland N, Mallick S, Patterson N, Roodenberg SA, et al. (December 2015). "Genome-wide patterns of selection in 230 ancient Eurasians". Nature. 528 (7583): 499–503. Bibcode:2015Natur.528..499M. doi:10.1038/nature16152. PMC   4918750 . PMID   26595274.
  20. ↑ Posth C, Nakatsuka N, Lazaridis I, Skoglund P, Mallick S, Lamnidis TC, et al. (November 2018). "Reconstructing the Deep Population History of Central and South America". Cell. 175 (5). Elsevier BV: 1185–1197.e22. doi:10.1016/j.cell.2018.10.027. hdl:10550/67985. PMC   6327247 . PMID   30415837.
  21. ↑ Wang, Chuan-Chao (March 2021). "Genomic insights into the formation of human populations in East Asia". Nature. 591 (7850): 413–419. Bibcode:2021Natur.591..413W. doi:10.1038/s41586-021-03336-2. ISSN   1476-4687. PMC   7993749 . PMID   33618348. "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."

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