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"ASPM" is an acronym for "'''A'''bnormal '''Sp'''indle-like, '''M'''icrocephaly-associated", which reflects its being an [[ortholog]] to the ''[[Drosophila melanogaster]]'' "abnormal spindle" (''asp'') gene. The [[gene expression|expressed]] protein product of the asp gene is essential for normal [[spindle apparatus|mitotic spindle]] function in embryonic [[neuroblast]]s and regulation of neurogenesis.<ref name="pmid12355089"/><ref name="pmid15972725">{{cite journal | vauthors = Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, Mochida GH, Risinger JI, Goldsmith P, Gunsior M, Solomon G, Gersch W, Kim JH, Barrett JC, Walsh CA, Jurka J, Masumoto H, Larionov V | display-authors = 6 | title = The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein | journal = Human Molecular Genetics | volume = 14 | issue = 15 | pages = 2155–65 | year = 2005 | pmid = 15972725 | doi = 10.1093/hmg/ddi220 }}</ref> | "ASPM" is an acronym for "'''A'''bnormal '''Sp'''indle-like, '''M'''icrocephaly-associated", which reflects its being an [[ortholog]] to the ''[[Drosophila melanogaster]]'' "abnormal spindle" (''asp'') gene. The [[gene expression|expressed]] protein product of the asp gene is essential for normal [[spindle apparatus|mitotic spindle]] function in embryonic [[neuroblast]]s and regulation of neurogenesis.<ref name="pmid12355089"/><ref name="pmid15972725">{{cite journal | vauthors = Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, Mochida GH, Risinger JI, Goldsmith P, Gunsior M, Solomon G, Gersch W, Kim JH, Barrett JC, Walsh CA, Jurka J, Masumoto H, Larionov V | display-authors = 6 | title = The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein | journal = Human Molecular Genetics | volume = 14 | issue = 15 | pages = 2155–65 | year = 2005 | pmid = 15972725 | doi = 10.1093/hmg/ddi220 }}</ref> | ||
A new allele of ASPM arose sometime in the | A new allele of ASPM arose sometime in the past 14,000 years (mean estimate 5,800 years), during the [[Holocene]], it seems to have swept through much of the European and Middle-Eastern population. Although the new allele is evidently beneficial, researchers do not know what it does. | ||
== Animal studies == | == Animal studies == | ||
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== Evolution == | == Evolution == | ||
A new [[allele]] (version) of ASPM appeared sometime | A new [[allele]] (version) of ASPM appeared sometime within the last 14,100 years, with a mean estimate of 5,800 years ago. The new allele has a frequency of about 50% in populations of the Middle East and Europe, it is less frequent in East Asia, and has low frequencies among Sub-Saharan African populations.<ref name="pmid16151009">{{cite journal | vauthors = Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT | display-authors = 6 | title = Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans | journal = Science | volume = 309 | issue = 5741 | pages = 1717–20 | date = Sep 2005 | pmid = 16151009 | doi = 10.1126/science.1113722 | laysummary = https://www.nytimes.com/2005/09/08/science/08cnd-brain.html?ex=1283832000&en=631902c8dabfb269&ei=5090&partner=rssuserland&emc=rss | laysource = New York Times: Researchers Say Human Brain Is Still Evolving | bibcode = 2005Sci...309.1717E }}</ref> It is also found with an unusually high percentage among the people of [[Papua New Guinea]], with a 59.4% occurrence.<ref name="pmid16151010"/> | ||
The mean estimated age of the ASPM allele of 5,800 years ago, roughly correlates with the development of written language, spread of agriculture and development of cities.<ref>Per the 2006 [[Discovery Channel]]/[[Channel 4]] documentary series ''What Makes Us Human?''</ref> Currently, two alleles of this gene exist: the older (pre-5,800 years ago) and the newer (post-5,800 years ago). About 10% of humans have two copies of the new ASPM allele, while about 50% have two copies of the old allele. The other 40% of humans have one copy of each. Of those with an instance of the new allele, 50% of them are an identical copy.<ref>{{cite journal | vauthors = Inman M | title = Human brains enjoy ongoing evolution | journal = New Scientist | volume = | issue = | pages = | year = 2005 | url = https://www.newscientist.com/article.ns?id=dn7974 }}<br/>{{cite journal | vauthors = Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT | display-authors = 6 | title = Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans | journal = Science | volume = 309 | issue = 5741 | pages = 1717–20 | date = Sep 2005 | pmid = 16151009 | doi = 10.1126/science.1113722 | bibcode = 2005Sci...309.1717E }}</ref> The allele affects genotype over a large (62 kbp) region, a so called [[selective sweep]] which signals a rapid spread of a mutation (such as the new ASPM) through the population; this indicates that the mutation is somehow advantageous to the individual.<ref name="pmid16151010">{{cite journal | vauthors = Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, Tishkoff SA, Lahn BT | display-authors = 6 | title = Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens | journal = Science | volume = 309 | issue = 5741 | pages = 1720–2 | date = Sep 2005 | pmid = 16151010 | doi = 10.1126/science.1116815 | bibcode = 2005Sci...309.1720M }}</ref><ref name="pmid16840683">{{cite journal | vauthors = Currat M, Excoffier L, Maddison W, Otto SP, Ray N, Whitlock MC, Yeaman S | display-authors = 6 | title = Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans" | journal = Science | volume = 313 | issue = 5784 | pages = 172; author reply 172 | date = Jul 2006 | pmid = 16840683 | doi = 10.1126/science.1122712 }}</ref> | The mean estimated age of the ASPM allele of 5,800 years ago, roughly correlates with the development of written language, spread of agriculture and development of cities.<ref>Per the 2006 [[Discovery Channel]]/[[Channel 4]] documentary series ''What Makes Us Human?''</ref> Currently, two alleles of this gene exist: the older (pre-5,800 years ago) and the newer (post-5,800 years ago). About 10% of humans have two copies of the new ASPM allele, while about 50% have two copies of the old allele. The other 40% of humans have one copy of each. Of those with an instance of the new allele, 50% of them are an identical copy.<ref>{{cite journal | vauthors = Inman M | title = Human brains enjoy ongoing evolution | journal = New Scientist | volume = | issue = | pages = | year = 2005 | url = https://www.newscientist.com/article.ns?id=dn7974 }}<br/>{{cite journal | vauthors = Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT | display-authors = 6 | title = Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans | journal = Science | volume = 309 | issue = 5741 | pages = 1717–20 | date = Sep 2005 | pmid = 16151009 | doi = 10.1126/science.1113722 | bibcode = 2005Sci...309.1717E }}</ref> The allele affects genotype over a large (62 kbp) region, a so called [[selective sweep]] which signals a rapid spread of a mutation (such as the new ASPM) through the population; this indicates that the mutation is somehow advantageous to the individual.<ref name="pmid16151010">{{cite journal | vauthors = Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, Tishkoff SA, Lahn BT | display-authors = 6 | title = Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens | journal = Science | volume = 309 | issue = 5741 | pages = 1720–2 | date = Sep 2005 | pmid = 16151010 | doi = 10.1126/science.1116815 | bibcode = 2005Sci...309.1720M }}</ref><ref name="pmid16840683">{{cite journal | vauthors = Currat M, Excoffier L, Maddison W, Otto SP, Ray N, Whitlock MC, Yeaman S | display-authors = 6 | title = Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans" | journal = Science | volume = 313 | issue = 5784 | pages = 172; author reply 172 | date = Jul 2006 | pmid = 16840683 | doi = 10.1126/science.1122712 }}</ref> | ||
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Testing the IQ of those with and without new ASPM allele has shown no difference in average IQ, providing no evidence to support the notion that the gene increases intelligence.<ref name="pmid16840683"/><ref name="pmid16687438">{{cite journal | vauthors = Woods RP, Freimer NB, De Young JA, Fears SC, Sicotte NL, Service SK, Valentino DJ, Toga AW, Mazziotta JC | display-authors = 6 | title = Normal variants of Microcephalin and ASPM do not account for brain size variability | journal = Human Molecular Genetics | volume = 15 | issue = 12 | pages = 2025–9 | date = Jun 2006 | pmid = 16687438 | doi = 10.1093/hmg/ddl126 }}</ref><ref name="pmid17220170">{{cite journal | vauthors = Mekel-Bobrov N, Posthuma D, Gilbert SL, Lind P, Gosso MF, Luciano M, Harris SE, Bates TC, Polderman TJ, Whalley LJ, Fox H, Starr JM, Evans PD, Montgomery GW, Fernandes C, Heutink P, Martin NG, Boomsma DI, Deary IJ, Wright MJ, de Geus EJ, Lahn BT | display-authors = 6 | title = The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence | journal = Human Molecular Genetics | volume = 16 | issue = 6 | pages = 600–8 | date = Mar 2007 | pmid = 17220170 | doi = 10.1093/hmg/ddl487 }}</ref> However statistical analysis has shown that the older forms of the gene are found more heavily in populations that speak [[tonal language]]s like [[Chinese language|Chinese]] or many Sub-Saharan [[African languages]].<ref name="pmid17537923">{{cite journal | vauthors = Dediu D, Ladd DR | title = Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 26 | pages = 10944–9 | date = Jun 2007 | pmid = 17537923 | pmc = 1904158 | doi = 10.1073/pnas.0610848104 | laysummary = https://www.newscientist.com/article/dn11939-genes-may-help-people-learn-chinese-.html | laysource = New Scientist: Genes may help people learn Chinese | bibcode = 2007PNAS..10410944D }}</ref> | Testing the IQ of those with and without new ASPM allele has shown no difference in average IQ, providing no evidence to support the notion that the gene increases intelligence.<ref name="pmid16840683"/><ref name="pmid16687438">{{cite journal | vauthors = Woods RP, Freimer NB, De Young JA, Fears SC, Sicotte NL, Service SK, Valentino DJ, Toga AW, Mazziotta JC | display-authors = 6 | title = Normal variants of Microcephalin and ASPM do not account for brain size variability | journal = Human Molecular Genetics | volume = 15 | issue = 12 | pages = 2025–9 | date = Jun 2006 | pmid = 16687438 | doi = 10.1093/hmg/ddl126 }}</ref><ref name="pmid17220170">{{cite journal | vauthors = Mekel-Bobrov N, Posthuma D, Gilbert SL, Lind P, Gosso MF, Luciano M, Harris SE, Bates TC, Polderman TJ, Whalley LJ, Fox H, Starr JM, Evans PD, Montgomery GW, Fernandes C, Heutink P, Martin NG, Boomsma DI, Deary IJ, Wright MJ, de Geus EJ, Lahn BT | display-authors = 6 | title = The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence | journal = Human Molecular Genetics | volume = 16 | issue = 6 | pages = 600–8 | date = Mar 2007 | pmid = 17220170 | doi = 10.1093/hmg/ddl487 }}</ref> However statistical analysis has shown that the older forms of the gene are found more heavily in populations that speak [[tonal language]]s like [[Chinese language|Chinese]] or many Sub-Saharan [[African languages]].<ref name="pmid17537923">{{cite journal | vauthors = Dediu D, Ladd DR | title = Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 26 | pages = 10944–9 | date = Jun 2007 | pmid = 17537923 | pmc = 1904158 | doi = 10.1073/pnas.0610848104 | laysummary = https://www.newscientist.com/article/dn11939-genes-may-help-people-learn-chinese-.html | laysource = New Scientist: Genes may help people learn Chinese | bibcode = 2007PNAS..10410944D }}</ref> | ||
Other genes related to brain development appear to have come under selective pressure in different populations. | |||
The [[DAB1]] gene, involved in organizing cell layers in the cerebral cortex, shows evidence of a selective sweep in the [[Chinese people|Chinese]]. The [[SV2B]] gene, which encodes a synaptic vesicle protein, likewise shows evidence of a selective sweep in [[African-Americans]].<ref name="url PLoS">{{cite journal | vauthors = Williamson SH, Hubisz MJ, Clark AG, Payseur BA, Bustamante CD, Nielsen R | title = Localizing recent adaptive evolution in the human genome | journal = PLoS Genetics | volume = 3 | issue = 6 | pages = e90 | year = 2007 | pmid = 17542651 | pmc = 1885279 | doi = 10.1371/journal.pgen.0030090 | url = }}</ref><ref name="url_NYT">{{cite web | url = https://www.nytimes.com/2007/06/26/science/26human.html?pagewanted=1&_r=3&ex=1340596800 | title = Humans Have Spread Globally, and Evolved Locally | vauthors = Wade N | date = 2007-06-26 | work = | publisher = New York Times | accessdate = 2009-08-01}}</ref> | |||
The [[DAB1]] gene, involved in organizing cell layers in the cerebral cortex, | |||
== See also == | == See also == | ||
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{{DEFAULTSORT:Aspm (Gene)}} | {{DEFAULTSORT:Aspm (Gene)}} | ||
[[Category:Developmental neuroscience]] | [[Category:Developmental neuroscience]] | ||
Latest revision as of 11:24, 3 January 2019
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Abnormal spindle-like microcephaly-associated protein also known as abnormal spindle protein homolog or Asp homolog is a protein that in humans is encoded by the ASPM gene.[1] ASPM is located on chromosome 1, band q31 (1q31).[2] Defective forms of the ASPM gene are associated with autosomal recessive primary microcephaly.[1][3]
"ASPM" is an acronym for "Abnormal Spindle-like, Microcephaly-associated", which reflects its being an ortholog to the Drosophila melanogaster "abnormal spindle" (asp) gene. The expressed protein product of the asp gene is essential for normal mitotic spindle function in embryonic neuroblasts and regulation of neurogenesis.[2][4]
A new allele of ASPM arose sometime in the past 14,000 years (mean estimate 5,800 years), during the Holocene, it seems to have swept through much of the European and Middle-Eastern population. Although the new allele is evidently beneficial, researchers do not know what it does.
Animal studies
The mouse gene, Aspm, is expressed in the primary sites of prenatal cerebral cortical neurogenesis. The difference between Aspm and ASPM is a single, large insertion coding for so-called IQ domains.[5] Studies in mice also suggest a role of the expressed Aspm gene product in mitotic spindle regulation.[6] The function is conserved, the C. elegans protein ASPM-1 was shown to be localized to spindle asters, where it regulates spindle organization and rotation by interacting with calmodulin, dynein and NuMA-related LIN-5.[7]
Evolution
A new allele (version) of ASPM appeared sometime within the last 14,100 years, with a mean estimate of 5,800 years ago. The new allele has a frequency of about 50% in populations of the Middle East and Europe, it is less frequent in East Asia, and has low frequencies among Sub-Saharan African populations.[8] It is also found with an unusually high percentage among the people of Papua New Guinea, with a 59.4% occurrence.[9]
The mean estimated age of the ASPM allele of 5,800 years ago, roughly correlates with the development of written language, spread of agriculture and development of cities.[10] Currently, two alleles of this gene exist: the older (pre-5,800 years ago) and the newer (post-5,800 years ago). About 10% of humans have two copies of the new ASPM allele, while about 50% have two copies of the old allele. The other 40% of humans have one copy of each. Of those with an instance of the new allele, 50% of them are an identical copy.[11] The allele affects genotype over a large (62 kbp) region, a so called selective sweep which signals a rapid spread of a mutation (such as the new ASPM) through the population; this indicates that the mutation is somehow advantageous to the individual.[9][12]
Testing the IQ of those with and without new ASPM allele has shown no difference in average IQ, providing no evidence to support the notion that the gene increases intelligence.[12][13][14] However statistical analysis has shown that the older forms of the gene are found more heavily in populations that speak tonal languages like Chinese or many Sub-Saharan African languages.[15]
Other genes related to brain development appear to have come under selective pressure in different populations. The DAB1 gene, involved in organizing cell layers in the cerebral cortex, shows evidence of a selective sweep in the Chinese. The SV2B gene, which encodes a synaptic vesicle protein, likewise shows evidence of a selective sweep in African-Americans.[16][17]
See also
References
- ↑ 1.0 1.1 Pattison L, Crow YJ, Deeble VJ, Jackson AP, Jafri H, Rashid Y, et al. (Dec 2000). "A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31". American Journal of Human Genetics. 67 (6): 1578–80. doi:10.1086/316910. PMC 1287934. PMID 11078481.
- ↑ 2.0 2.1 Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, et al. (Oct 2002). "ASPM is a major determinant of cerebral cortical size". Nature Genetics. 32 (2): 316–20. doi:10.1038/ng995. PMID 12355089.
- ↑ Kaindl AM, Passemard S, Kumar P, Kraemer N, Issa L, Zwirner A, et al. (2010). "Many roads lead to primary autosomal recessive microcephaly". Progress in Neurobiology. 90 (3): 363–83. doi:10.1016/j.pneurobio.2009.11.002. PMID 19931588.
- ↑ Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, et al. (2005). "The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein". Human Molecular Genetics. 14 (15): 2155–65. doi:10.1093/hmg/ddi220. PMID 15972725.
- ↑ Bähler M, Rhoads A (Feb 2002). "Calmodulin signaling via the IQ motif". FEBS Letters. 513 (1): 107–13. doi:10.1016/S0014-5793(01)03239-2. PMID 11911888.
- ↑ Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB (Jul 2006). "Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells". Proceedings of the National Academy of Sciences of the United States of America. 103 (27): 10438–43. Bibcode:2006PNAS..10310438F. doi:10.1073/pnas.0604066103. PMC 1502476. PMID 16798874.
- ↑ van der Voet M, Berends CW, Perreault A, Nguyen-Ngoc T, Gönczy P, Vidal M, et al. (Mar 2009). "NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha". Nature Cell Biology. 11 (3): 269–77. doi:10.1038/ncb1834. PMID 19219036.
- ↑ Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, et al. (Sep 2005). "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans". Science. 309 (5741): 1717–20. Bibcode:2005Sci...309.1717E. doi:10.1126/science.1113722. PMID 16151009. Lay summary – New York Times: Researchers Say Human Brain Is Still Evolving.
- ↑ 9.0 9.1 Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, et al. (Sep 2005). "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens". Science. 309 (5741): 1720–2. Bibcode:2005Sci...309.1720M. doi:10.1126/science.1116815. PMID 16151010.
- ↑ Per the 2006 Discovery Channel/Channel 4 documentary series What Makes Us Human?
- ↑ Inman M (2005). "Human brains enjoy ongoing evolution". New Scientist.
Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, et al. (Sep 2005). "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans". Science. 309 (5741): 1717–20. Bibcode:2005Sci...309.1717E. doi:10.1126/science.1113722. PMID 16151009. - ↑ 12.0 12.1 Currat M, Excoffier L, Maddison W, Otto SP, Ray N, Whitlock MC, et al. (Jul 2006). "Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans"". Science. 313 (5784): 172, author reply 172. doi:10.1126/science.1122712. PMID 16840683.
- ↑ Woods RP, Freimer NB, De Young JA, Fears SC, Sicotte NL, Service SK, et al. (Jun 2006). "Normal variants of Microcephalin and ASPM do not account for brain size variability". Human Molecular Genetics. 15 (12): 2025–9. doi:10.1093/hmg/ddl126. PMID 16687438.
- ↑ Mekel-Bobrov N, Posthuma D, Gilbert SL, Lind P, Gosso MF, Luciano M, et al. (Mar 2007). "The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence". Human Molecular Genetics. 16 (6): 600–8. doi:10.1093/hmg/ddl487. PMID 17220170.
- ↑ Dediu D, Ladd DR (Jun 2007). "Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin". Proceedings of the National Academy of Sciences of the United States of America. 104 (26): 10944–9. Bibcode:2007PNAS..10410944D. doi:10.1073/pnas.0610848104. PMC 1904158. PMID 17537923. Lay summary – New Scientist: Genes may help people learn Chinese.
- ↑ Williamson SH, Hubisz MJ, Clark AG, Payseur BA, Bustamante CD, Nielsen R (2007). "Localizing recent adaptive evolution in the human genome". PLoS Genetics. 3 (6): e90. doi:10.1371/journal.pgen.0030090. PMC 1885279. PMID 17542651.
- ↑ Wade N (2007-06-26). "Humans Have Spread Globally, and Evolved Locally". New York Times. Retrieved 2009-08-01.
External links
- GeneReviews/NCBI/NIH/UW entry on Primary Autosomal Recessive Microcephaly
- Human ASPM genome location and ASPM gene details page in the UCSC Genome Browser.