ASPM (asp (abnormal spindle) homolog, microcephaly associated)

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The ASPM gene is the human equivalent of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is known to be essential for normal mitotic spindle function in embryonic neuroblasts.  The mouse Aspm gene is also known to be expressed specifically in the  sites of prenatal cerebral cortical neurogenesis.  Inactivation of this gene in humans results in a severe condition called microcephaly, i.e. a small brain, associated with mental retardation. As human evolution is characterized by a dramatic increase in brain size, one group evaulated this gene and reported that it had undergone significantly higher rates of protein sequence evolution in primates than in rodents. Furthermore, they reported that ASPM has undergone even more rapid evolution in humans,  including evidence of a selective sweep in human populations. However, several aspects of these findings have been debated by other groups. Regardless, it is interesting that a gene that is associated with a small brain when it is damaged in humans, may have also shown increased evolution in humans.

Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Gene Symbol Type of Human-Specific Changes
ASPM Accelerated Evolution

References

  1. Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens"., Yu, Fuli, R Hill Sean, Schaffner Stephen F., Sabeti Pardis C., Wang Eric T., Mignault Andre A., Ferland Russell J., Moyzis Robert K., Walsh Christopher A., and Reich David , Science, 2007 Apr 20, Volume 316, Issue 5823, p.370, (2007)
  2. 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"., Currat, Mathias, Excoffier Laurent, Maddison Wayne, Otto Sarah P., Ray Nicolas, Whitlock Michael C., and Yeaman Sam , Science, 2006 Jul 14, Volume 313, Issue 5784, p.172; author reply 172, (2006)
  3. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens., Mekel-Bobrov, Nitzan, Gilbert Sandra L., Evans Patrick D., Vallender Eric J., Anderson Jeffrey R., Hudson Richard R., Tishkoff Sarah A., and Lahn Bruce T. , Science, 2005 Sep 9, Volume 309, Issue 5741, p.1720-2, (2005)
  4. Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans., Evans, Patrick D., Anderson Jeffrey R., Vallender Eric J., Gilbert Sandra L., Malcom Christine M., Dorus Steve, and Lahn Bruce T. , Hum Mol Genet, 2004 Mar 1, Volume 13, Issue 5, p.489-94, (2004)
  5. Protein-truncating mutations in ASPM cause variable reduction in brain size., Bond, Jacquelyn, Scott Sheila, Hampshire Daniel J., Springell Kelly, Corry Peter, Abramowicz Marc J., Mochida Ganesh H., Hennekam Raoul C. M., Maher Eamonn R., Fryns Jean-Pierre, et al. , Am J Hum Genet, 2003 Nov, Volume 73, Issue 5, p.1170-7, (2003)
  6. ASPM is a major determinant of cerebral cortical size., Bond, Jacquelyn, Roberts Emma, Mochida Ganesh H., Hampshire Daniel J., Scott Sheila, Askham Jonathan M., Springell Kelly, Mahadevan Meera, Crow Yanick J., Markham Alexander F., et al. , Nat Genet, 2002 Oct, Volume 32, Issue 2, p.316-20, (2002)