ASPM (gene)

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. ASPM is located on chromosome 1, band q31 (1q31). Defective forms of the ASPM gene are associated with autosomal recessive primary microcephaly.

"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.

A new allele of ASPM arose sometime in the last 15000 years, and 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. Studies in mice also suggest a role of the expressed Aspm gene product in mitotic spindle regulation. 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.

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. It is also found with an unusually high percentage among the people of Papua New Guinea, with a 59.4% occurrence.

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. 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. 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.

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. 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.

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.

See also

• Microcephalin

External links

• GeneReviews/NCBI/NIH/UW entry on Primary Autosomal Recessive Microcephaly