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

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MOCA Domain: 
Genetics
MOCA Topic Authors: 
Majesta O'Bleness
James Sikela

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:
ASPM (ASPM: asp (abnormal spindle) homolog, microcephaly associated (Drosophila))
Type of Human-Specific Changes:
Accelerated Evolution
Related MOCA Topics
References: 

Bond, J.; Roberts, E.; Mochida, G. H.; Hampshire, D. J.; Scott, S.; Askham, J. M.; Springell, K.; Mahadevan, M.; Crow, Y. J.; Markham, A. F.; Walsh, C. A.; Woods, C. G. :ASPM is a major determinant of cerebral cortical size. Nature Genet. 32: 316-320, 2002.PubMed ID : 12355089

 

Bond, J.; Scott, S.; Hampshire, D. J.; Springell, K.; Corry, P.; Abramowicz, M. J.; Mochida, G. H.; Hennekam, R. C. M.; Maher, E. R.; Fryns, J.-P.; Alswaid, A.; Jafri, H.; Rashid, Y.; Mubaidin, A.; Walsh, C. A.; Roberts, E.; Woods, C. G. :
Protein-truncating mutations in ASPM cause variable reduction in brain size. Am. J. Hum. Genet. 73: 1170-1177, 2003.
PubMed ID : 14574646

 

Evans, P. D.; Anderson, J. R.; Vallender, E. J.; Gilbert, S. L.; Malcom, C. M.; Dorus, S.; Lahn, B. T. :Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Hum. Molec. Genet. 13: 489-494, 2004.PubMed ID : 1472215

 

Mekel-Bobrov, N.; Gilbert, S. L.; Evans, P. D.; Vallender, E. J.; Anderson, J. R.; Hudson, R. R.; Tishkoff, S. A.; Lahn, B. T. : Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309: 1720-1722, 2005. PubMed ID : 1615101

 

Currat, M.; Excoffier, L.; Maddison, W.; Otto, S. P.; Ray, N.; Whitlock, M. C.; Yeaman, S. :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.' (Abstract) Science 313: 172 only, 2006.PubMed ID : 1684068

 

Mekel-Bobrov, N.; Evans, P. D.; Gilbert, S. L.; Vallender, E. J.; Hudson, R. R.; Lahn, B. T. :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.' (Abstract) Science 313: 172 only, 2006.PubMed ID : 16840683

 

Yu, F.; Hill, R. S.; Schaffner, S. F.; Sabeti, P. C.; Wang, E. T.; Mignault, A. A.; Ferland, R. J.; Moyzis, R. K.; Walsh, C. A.; Reich, D. :Comment on 'Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens.' Science 316: 370 only, 2007.PubMed ID : 17446375