ASPM (gene)

Abnormal spindle microtubule assembly
Identifiers
Symbols ASPM ; ASP; Calmbp1; MCPH5
External IDs OMIM: 605481 MGI: 1334448 HomoloGene: 7650 GeneCards: ASPM Gene
Orthologs
Species Human Mouse
Entrez 259266 12316
Ensembl ENSG00000066279 ENSMUSG00000033952
UniProt Q8IZT6 Q8CJ27
RefSeq (mRNA) NM_001206846 NM_009791
RefSeq (protein) NP_001193775 NP_033921
Location (UCSC) Chr 1:
197.08 – 197.15 Mb		 Chr 1:
139.45 – 139.49 Mb
PubMed search

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]

"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.[2]

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.[3] Studies in mice also suggest a role of the expressed Aspm gene product in mitotic spindle regulation.[4] 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.[5]

Evolution

A new allele (version) of ASPM appeared sometime between 14,100 and 500 years ago 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.[6] It is also found with an unusually high percentage among the people of Papua New Guinea, with a 59.4% occurrence.[7]

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.[8] 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.[9] 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.[7][10]

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.[10][11][12] 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.[13]

Diversity

The DAB1 gene, involved in organizing cell layers in the cerebral cortex, appears to have come under selection in the Chinese. The SV2B gene, which encodes a synaptic vesicle protein, likewise appears to have undergone a selective sweep among African-Americans.[14][15]

See also

References

  1. 1 2 Pattison L, Crow YJ, Deeble VJ, Jackson AP, Jafri H, Rashid Y, Roberts E, Woods CG (December 2000). "A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31". Am. J. Hum. Genet. 67 (6): 1578–80. doi:10.1086/316910. PMC 1287934. PMID 11078481.
  2. 1 2 Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG (October 2002). "ASPM is a major determinant of cerebral cortical size". Nat. Genet. 32 (2): 316–20. doi:10.1038/ng995. PMID 12355089.
  3. ↑ Bähler M, Rhoads A (February 2002). "Calmodulin signaling via the IQ motif". FEBS Lett. 513 (1): 107–13. doi:10.1016/S0014-5793(01)03239-2. PMID 11911888.
  4. ↑ Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB (July 2006). "Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells". Proc. Natl. Acad. Sci. U.S.A. 103 (27): 10438–43. Bibcode:2006PNAS..10310438F. doi:10.1073/pnas.0604066103. PMC 1502476. PMID 16798874.
  5. ↑ van der Voet, Monique; Berends, Christian W. H.; Perreault, Audrey; Nguyen-Ngoc, Tu; Gönczy, Pierre; Vidal, Marc; Boxem, Mike; van den Heuvel, Sander (2009). "NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Gα". Nature Cell Biology 11 (3): 269–277. doi:10.1038/ncb1834. ISSN 1465-7392.
  6. ↑ Evans PD, Gilbert SL, Mekel-Bobrov N, Vallender EJ, Anderson JR, Vaez-Azizi LM, Tishkoff SA, Hudson RR, Lahn BT (September 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.
  7. 1 2 Mekel-Bobrov N, Gilbert SL, Evans PD, Vallender EJ, Anderson JR, Hudson RR, Tishkoff SA, Lahn BT (September 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.
  8. ↑ Per the 2006 Discovery Channel/Channel 4 documentary series What Makes Us Human?
  9. ↑ Inman M (2005). "Human brains enjoy ongoing evolution". New Scientist.
    Evans PD, Gilbert SL, Mekel-Bobrov N; et al. (September 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.
  10. 1 2 Currat M, Excoffier L, Maddison W, Otto SP, Ray N, Whitlock MC, Yeaman S (July 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.
  11. ↑ Woods RP, Freimer NB, De Young JA, Fears SC, Sicotte NL, Service SK, Valentino DJ, Toga AW, Mazziotta JC (June 2006). "Normal variants of Microcephalin and ASPM do not account for brain size variability". Hum. Mol. Genet. 15 (12): 2025–9. doi:10.1093/hmg/ddl126. PMID 16687438.
  12. ↑ 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 (March 2007). "The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence". Hum. Mol. Genet. 16 (6): 600–8. doi:10.1093/hmg/ddl487. PMID 17220170.
  13. ↑ Dediu D, Ladd DR (June 2007). "Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin". Proc. Natl. Acad. Sci. U.S.A. 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.
  14. ↑ Williamson, S. H.; et al. (1 June 2007). "Localizing Recent Adaptice Evolution in the Human Genome -". PLoS. Retrieved 23 May 2012.
  15. ↑ Wade N (2007-06-26). "Humans Have Spread Globally, and Evolved Locally -". New York Times. Retrieved 2009-08-01.

External links

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