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microcephaly, primary autosomal recessive 1
Symbol MCPH1
Alt. Symbols Microcephalin[1], BRIT1[2]
Entrez 79648
HUGO 6954
OMIM 607117
UniProt Q8NEM0
Other data
Locus Chr. 8 p23
microcephaly, primary autosomal recessive 2
Symbol MCPH2
Entrez 4181
HUGO 6955
OMIM 604317
Other data
Locus Chr. 19 q13.1-13.2
microcephaly, primary autosomal recessive 3
Symbol CDK5RAP2
Alt. Symbols MCPH3
Entrez 23702
HUGO 6956
OMIM 604804
Other data
Locus Chr. 9 q33.3
microcephaly, primary autosomal recessive 4
Symbol MCPH4
Entrez 23701
HUGO 6957
OMIM 604321
Other data
Locus Chr. 15 q15-21
microcephaly, primary autosomal recessive 5
Symbol ASPM
Alt. Symbols MCPH5
Entrez 64590
HUGO 6958
OMIM 608716
Other data
Locus Chr. 1 q31
microcephaly, primary autosomal recessive 6
Symbol CENPJ
Alt. Symbols MCPH6
Entrez 170629
HUGO 17120
OMIM 608393
Other data
Locus Chr. 13 q12.2

Microcephalin (MCPH1) is one of six genes causing primary microcephaly (Online 'Mendelian Inheritance in Man' (OMIM) 251200) when non-functional mutations exist in the homozygous state. Derived from the Greek words for "small" and "head", this condition is characterised by a severely diminished brain.[3][1] Hence it has been assumed that normal variants have a role in brain development.[4][5] But no effect on mental ability, brain size or behavior is attributable to either this or another similarly studied microcephaly gene, ASPM.[6] [7]


Expression in the brain

MCPH1 is expressed in the fetal brain, in the developing forebrain, and on the walls of the lateral ventricles. Cells of this area divide, producing neurons that migrate to eventually form the cerebral cortex.


A derived form of MCPH1 called haplogroup D appeared about 37,000 years ago (anytime between 14,000 and 60,000 years ago) and has spread to become the more common form throughout the world except Sub-Saharan Africa. The timing of its emergence may have closely preceded the Upper Paleolithic, when people started colonising Europe, although the margin of error is substantial[8] and there is evidence that the transition to the Upper Paleolithic occurred in Africa before spreading to Europe.[9] Doubts concerning origins aside, modern distributions of chromosomes bearing the ancestral forms of MCPH1 and MCPH5 coincide with the incidence of tonal languages, although the nature of this relationship can only be guessed at.[10]

Haplogroup D may have originated from a lineage separated from modern humans approximately 1.1 million years ago and later introgressed into humans. This finding supports the possibility of admixture between modern humans and extinct Homo spp. (Neanderthals being one possibility).[11] On the other hand the sample of 89 individuals with only nine Africans used in the study has been criticized as being inadequate for the conclusion the paper draws, and comparable studies demonstrate that undersampling specific areas of East/Central Africa may lead to unwarranted conclusions.[12] Additionally, scientists have not identified the evolutionary pressures that caused the supposed spread of these mutations.[13]


Although Chinese himself, Bruce Lahn's public announcements some brain-genes are more advanced on some continents than on others were conscripted by websites promoting white "racialism". An American xenophobic magazine embraced the research as "the moment the antiracists and egalitarians have dreaded." The National Review Online, wrote that as a result of the findings, "our cherished national dream of a well-mixed and harmonious meritocracy may be unattainable."

Lahn's study began to attract considerable controversy in the science world, where he was criticized for overinterpreting and sensationalizing his findings. One of the co-authors, Sarah Tishkoff, distanced herself from the study saying that she was bothered how the paper drew a link between the genetic changes and the rise of civilization. She felt that any conclusions about why the mutations spread were premature and that it is "very simplistic" to confer so many behavioural traits on a single gene. Richard Lewontin considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." All the while maintaining that the science of his studies were sound, Lahn has nevertheless conceded that there is no real evidence natural selection had acted on cognition or intelligence through the genes. Tainted by the experience, he is engaging himself with other areas of study.[14][15]

Other names

The microcephaly-related loci MCPH 3, 5 and 6 are usually classified by their alternate names CDK5RAP2, ASPM and CENPJ respectively, according to their other roles. (More information can be found from the articles dedicated to them and links in the information boxes.)

See also


  1. ^ a b Jackson, A.P., et al. (2002). "Identification of Microcephalin, a Protein Implicated in Determining the Size of the Human Brain". Am. J. Hum. Genet. 71: 136-142. PMID 12046007.
  2. ^ Lin, S.Y. & Elledge, S.J. (2003). "Multiple tumor suppressor pathways negatively regulate telomerase". Cell 113: 881-889. PMID 12837246.
  3. ^ Jackson, A.P., et al. (1998). "Primary Autosomal Recessive Microcephaly (MCPH1) Maps to Chromosome 8p22-pter". Am. J. Hum. Genet. 63: 541-546. PMID 9683597.
  4. ^ Wang, Y.Q. & B. Su (2004). "Molecular evolution of microcephalin, a gene determining human brain size". Hum. Mol. Genet. 13: 1131-1137. doi:10.1093/hmg/ddh127.
  5. ^ Evans, P.D., et al. (2004). "Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size". Hum. Mol. Genet. 13: 1139-1145. doi:10.1093/hmg/ddh126.
  6. ^ R.P. Woods, et al. (2006). "Normal variants of Microcephalin and ASPM do not account for brain size variability". Hum. Mol. Genet. 15 (12): 2025-2029. doi:10.1093/hmg/ddl126.
  7. ^ J.P. Rushton, P.A. Vernon & T.A. Bons (22 Apr., 2007). "No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism". Biol. Lett. 3 (2): 157-160. doi:10.1098/rsbl.2006.0586.
  8. ^ Evans, P.D., et al. (2005). "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans". Science 309: 1717-20. doi:10.1126/science.1113722. Lay summary – New York Times: Researchers Say Human Brain Is Still Evolving.
  9. ^ Ambrose, S.H. (1998). "Chronology of the Later Stone Age and food production in East Africa". J. Archaeol. Sci. 25 (4): 377-392. doi:10.1006/jasc.1997.0277. Lay summary – "Modern" Behavior Began 40,000 Years Ago In Africa, Evidence Suggests (Science
  10. ^ Dediu, D. & D.R. Ladd (2007). "Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin". Proc. Nat. Acad. Sci.. doi:10.1073/pnas.0610848104.
  11. ^ PNAS article Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage Published online before print November 7, 2006 by Proceedings of the National Academy of Sciences of the USA
  12. ^ Shimada MK, Panchapakesan K, Tishkoff SA, Nato AQ, Hey J (2007). "Divergent haplotypes and human history as revealed in a worldwide survey of X-linked DNA sequence variation". Mol. Biol. Evol. 24 (3): 687-98. doi:10.1093/molbev/msl196. PMID 17175528.
  13. ^ Mekel-Bobrov, N., et al. (2007). "The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence". Hum. Mol. Genet.: adv. access. doi:10.1093/hmg/ddl487.
  14. ^ scientists study of brain gene sparks a backlash
  15. ^ Balter, M. (Dec 2006). "Bruce Lahn profile: Brain man makes waves with claims of recent human evolution". Science 314 (5807): 1871 - 1873. doi:10.1126/science.314.5807.1871.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Microcephalin". A list of authors is available in Wikipedia.
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