ASPM (Gene)

protein
Name = Abnormal spindle-like, microcephaly associated gene
caption =


width =
HGNCid = 19048
Symbol = ASPM
AltSymbols = MCPH5
EntrezGene = 259266
OMIM = 605481
RefSeq = NM_018136
UniProt = Q8IZT6
PDB =
ECnumber =
Chromosome = 1
Arm = q
Band = 31
LocusSupplementaryData =

"ASPM" is a human gene whose defective forms 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. ASPM is located on chromosome 1, band q31 (1q31).

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.ref|IQDomain

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 percent in populations of the Middle East and Europe, it is less frequent in East Asia, and has low frequencies among Sub-Saharan African populations. [cite journal
author = Evans, P.D., "et al."
year = 2005
title = "Microcephalin", a gene regulating brain size, continues to evolve adaptively in humans
journal = Science
volume = 309
pages = 1717–20
doi = 10.1126/science.1113722
laysummary = http://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
pmid = 16151009]

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. [Per the 2006 Discovery Channel/Channel 4 documentary series "What Makes Us Human?"] 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 [cite journal |author=Inman M |title=Human brains enjoy ongoing evolution |journal=New Scientist |volume= |issue= |pages= |year=2005 |url=http://www.newscientist.com/article.ns?id=dn7974 cite journal |author=Evans PD, Gilbert SL, Mekel-Bobrov N, "et al" |title=Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans |journal=Science (journal) |volume=309 |issue=5741 |pages=1717–20 |year=2005 |month=Sep |pmid=16151009 |doi=10.1126/science.1113722 |url=] suggesting a highly rapid spread from the original mutation. According to a hypothesis called a "selective sweep", the rapid spread of a mutation (such as the new ASPM) through the population indicates that the mutation is somehow advantageous to the individual.ref|ScienceArticle1 As of today, there is no evidence to support the notion that the new ASPM allele increases intelligence, and some researchers dispute whether the spread of the allele even demonstrates selection [cite journal
author = Woods, R.P., "et al."
year = 2006
title = Normal variants of Microcephalin and ASPM do not account for brain size variability
journal = Hum. Mol. Genet.
volume = 15
issue = 12
pages = 2025–2029
doi = 10.1093/hmg/ddl126
pmid = 16687438] [cite journal
author = Mekel-Bobrov, N., "et al."
title = The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence
year = 2007
journal = Hum. Mol. Genet.
pages = 600
doi = 10.1093/hmg/ddl487| volume = 16
pmid = 17220170] ref|ScienceArticleref|NewsArticle. They suggest that the current distribution of the alleles could be explained by a founder effect, following an out of Africa dispersal. However, statistical analysis has shown that the older forms of the gene are found more heavily in populations that speak tonal languages like Chinese. [cite journal |author=Schultz N |title=Genes may help people learn Chinese |journal=New Scientist |volume= |issue= |pages= |year=2007 |url=http://www.newscientist.com/article/dn11939-genes-may-help-people-learn-chinese-.html cite journal |author=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=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=26 |pages=10944–9 |year=2007 |month=Jun |pmid=17537923 |pmc=1904158 |doi=10.1073/pnas.0610848104 |url=]

Diversity

Instead of ASPM, the DAB1 gene, which also increases the density of neural matter, appears to have come under selection in the Chinese. [ [http://www.nytimes.com/2007/06/26/science/26human.html?_r=2&pagewanted=2&ex=1340596800&oref=slogin New York Times article] ]

References

Notes

# An IQ domain is a segment of DNA that codes for the IQ motif.
#::IQ protein motif: [FILV] Qxxx [RK] Gxxx [RK] xx [FILVWY]
#:The term "IQ" refers to the first two amino acids of the motif: isoleucine (commonly) and glutamine (invariably).
# cite journal
author=Nitzan Mekel-Bobrov "et al."
title=Ongoing Adaptive Evolution of "ASPM", a Brain Size Determinant in Homo sapiens
journal=Science
year=2005
volume=309
issue=5741
pages=1720–2
doi= 10.1126/science.1116815
pmid=16151010
# cite journal
author=Mathias Currat "et al."
title=Comment on "Ongoing Adaptive Evolution of "ASPM", a Brain Size Determinant in Homo sapiens"
journal=Science
year=2006
volume=313
issue= 5784
pages=172
url=http://www.sciencemag.org/cgi/content/full/sci;313/5784/172a
pmid=16840683
doi=10.1126/science.1122712
# following is one of a large number of similar news articles:
#:cite web
title=Study Suggests Human Brains Still Evolving
work=Live Science: Human Biology
url=http://www.livescience.com/humanbiology/ap_050908_brain.html
accessdate=November 26
accessyear=2005
# Kniffin, Cassandra L. "et al." OMIM|605481|ABNORMAL SPINDLE-LIKE, MICROCEPHALY-ASSOCIATED; ASPM
#:cite web
title=Bruce Lahn moving on to non-IQ projects?
work=Live Science: Human Biology
url=http://www.gnxp.com/blog/2006/06/bruce-lahn-moving-on-to-non-iq.php
accessdate=June 16
accessyear=2006