Microcephalin: Difference between revisions

microcephaly, primary autosomal recessive 2
microcephaly, primary autosomal recessive 2
Identifiers
Symbol	MCPH2
NCBI gene	4181
HGNC	6955
OMIM	604317
Other data
Locus	Chr. 19 q13.1-13.2

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Structures	Swiss-model
Domains	InterPro

microcephaly, primary autosomal recessive 1
microcephaly, primary autosomal recessive 1
Identifiers
Symbol	MCPH1
NCBI gene	79648
HGNC	6954
OMIM	607117
UniProt	Q8NEM0
Other data
Locus	Chr. 8 p23
Structures
Search for
Structures	Swiss-model
Domains	InterPro

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microcephaly, primary autosomal recessive 3
Identifiers
Symbol	MCPH3
Alt. symbols	CDK5RAP2
NCBI gene	23702
HGNC	6956
OMIM	604804
Other data
Locus	Chr. 9 q33.3

microcephaly, primary autosomal recessive 4
Identifiers
Symbol	MCPH4
NCBI gene	23701
HGNC	6957
OMIM	604321
Other data
Locus	Chr. 15 q15-21

microcephaly, primary autosomal recessive 5
Identifiers
Symbol	MCPH5
Alt. symbols	ASPM
NCBI gene	64590
HGNC	6958
OMIM	608716
Other data
Locus	Chr. 1 q31

microcephaly, primary autosomal recessive 6
Identifiers
Symbol	MCPH6
Alt. symbols	CENPJ
NCBI gene	170629
HGNC	17120
OMIM	608393
Other data
Locus	Chr. 13 q12.2

The microcephalins (Greek for "small head) are a group of six genes (called MCPH1 to MCPH6), in which two copies of a loss-of-function mutation causes primary microcephaly (Online Mendelian Inheritance in Man (OMIM): 251200), a condition characterised by a severely diminished brain.^[1]^[2] Hence it has been assumed that normal variants of the these genes have a role in brain development,^[3]^[4] but evidence to support this is lacking so far^[5] and the selective pressures for the continual evolution of at least two of them are unknown.^[6]These genes were discovered by geneticists at the University of Chicago led by Bruce Lahn.

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.

Evolution

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. It is therefore very possible that the timing of its emergence narrowly preceded the Upper Paleolithic, when people started colonising Europe.^[7] The distribution of chromosomes bearing the ancestral forms of MCPH1 and MCPH5 coincide with the incidence of tonal languages, although the exact nature of the relationship is unknown.^[8]

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).^[9] On the other hand the sample of 89 individuals with only 9 Africans used in the study has been criticized as being inadequate for the conclusion the paper draws, and comparable studies demostrate that undersampling specific areas of East/Central Africa may lead to unwarranted conclusions.^[10]

Controversy

Websites promoting white racialism quickly seized on the evolutionary findings. One magazine called the discovery "the moment the antiracists and egalitarians have dreaded". Lahn's study drew much controversy. A member of his staff distanced herself from the study and funding for some of his other studies was withdrawn. Notable scientists such as Richard Lewontin and Spencer Wells criticized Lahn for making premature observations.^[11]^[12]

Other names

The microcephaly-related genes 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.

Sources and notes

^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ 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.
^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Woods, R.P.; 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)
^ 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.
^ 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
^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ scientists study of brain gene sparks a backlash
^ Brain Man Makes Waves With Claims of Recent Human Evolution

External links

Neanderthal Brains - a lecture by Bruce Lahn - from the NYAS podcasts.

@@ Line 167: / Line 167: @@
 | doi = 10.1093/hmg/ddl487}}
 </ref>These genes were discovered by geneticists at the University of Chicago led by [[Bruce Lahn]].
+== Expression in the brain ==
+MCPH1 is expressed in the fetal [[brain]], in the developing [[forebrain]], and on the walls of the [[lateral ventricles]]. [[cell (biology)|Cells]] of this area divide, producing [[neuron]]s that migrate to eventually form the [[cerebral cortex]].
 ==Evolution==
@@ Line 191: / Line 194: @@
 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 ''[[archaic Homo sapiens|Homo]]'' spp. ([[Neanderthal]]s being one possibility).<ref>[http://www.pnas.org/cgi/content/abstract/0606966103v1 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</ref> On the other hand the sample of 89 individuals with only 9 Africans used in the study has been criticized as being inadequate for the conclusion the paper draws, and comparable studies demostrate that undersampling specific areas of East/Central Africa may lead to unwarranted conclusions.<ref name="pmid17175528">{{cite journal |author=Shimada MK, Panchapakesan K, Tishkoff SA, Nato AQ, Hey J |title=Divergent haplotypes and human history as revealed in a worldwide survey of X-linked DNA sequence variation |journal=Mol. Biol. Evol. |volume=24 |issue=3 |pages=687-98 |year=2007 |pmid=17175528 |doi=10.1093/molbev/msl196 |issn=}}</ref>
-== Expression in the brain ==
-MCPH1 is expressed in the fetal [[brain]], in the developing [[forebrain]], and on the walls of the [[lateral ventricles]]. [[cell (biology)|Cells]] of this area divide, producing [[neuron]]s that migrate to eventually form the [[cerebral cortex]].
 ==Controversy==
+Websites promoting white racialism quickly seized on the evolutionary findings. One magazine called the discovery "the moment the antiracists and egalitarians have dreaded". Lahn's study drew much controversy. A member of his staff distanced herself from the study and funding for some of his other studies was withdrawn. Notable scientists such as [[Richard Lewontin]] and [[Spencer Wells]] criticized Lahn for making premature observations.<ref>[http://online.wsj.com/public/article/SB115040765329081636-T5DQ4jvnwqOdVvsP_XSVG_lvgik_20060628.html?mod=blogs scientists study of brain gene sparks a backlash]</ref><ref>[http://www.sciencemag.org/cgi/content/full/314/5807/1871 Brain Man Makes Waves With Claims of Recent Human Evolution]</ref>
-When Bruce Lahn, released his study on the Microcephalins, he stated that these genes had swept through most of the world except sub-saharan Africa. He added that the genes may have increased the  intelligence of Europeans and Asians and led to the upper paleolithic technology.
-Websites promoting white racialism quickly seized on these findings. One magazine stated the discovery as "the moment the antiracists and egalitarians have dreaded".
-Lahn drew much controversy. A member of his staff distanced herself from the study and funding for some of his other studies was withdrawn. Notable scientists such as [[Richard Lewontin]] and [[Spencer Wells]] criticized Lahn for making premature observations<ref>[http://online.wsj.com/public/article/SB115040765329081636-T5DQ4jvnwqOdVvsP_XSVG_lvgik_20060628.html?mod=blogs scientists study of brain gene sparks a backlash]</ref><ref>[http://www.sciencemag.org/cgi/content/full/314/5807/1871 Brain Man Makes Waves With Claims of Recent Human Evolution]</ref>.
 ==Other names==