Template:Short description Template:Infobox gene Template:Infobox protein family
Microcephalin (MCPH1) is a gene that is expressed during fetal brain development. Certain mutations in MCPH1, when homozygous, cause primary microcephaly—a severely diminished brain.<ref name = "microcephalin"/><ref>{{#ifeq:|none||{{#switch: | short = OMIM: | shortlink = OMIM: | plain = Online Mendelian Inheritance in Man: | full | #default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: |{{{2}}} - }} 251200</ref><ref name = "AutoR3-2"/> Hence, it has been assumed that variants have a role in brain development.<ref name = "AutoR3-3"/><ref name = "AutoR3-4"/> However, in normal individuals no effect on mental ability or behavior has yet been demonstrated in either this or another similarly studied microcephaly gene, ASPM.<ref name = "AutoR3-5"/><ref name = "AutoR3-6"/> However, an association has been established between normal variation in brain structure, as measured with MRI (i.e., primarily cortical surface area and total brain volume) but only in females, and common genetic variants within both the MCPH1 gene and another similarly studied microcephaly gene, CDK5RAP2.<ref name="Rimol_2010">Template:Cite journal</ref>
StructureEdit
Microcephalin proteins contain the following three domains:
- N-terminal BRCT domain
- Central microcephalin protein domain (Template:InterPro)
- C-terminal BRCT domain
Expression in the brainEdit
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.
EvolutionEdit
A derived form of MCPH1 appeared about 37,000 years ago (any time between 14,000 and 60,000 years ago) and has spread to become the most common form of microcephalin throughout the world except Sub-Saharan Africa; this rapid spread suggests a selective sweep.<ref name = "AutoR3-7"/><ref name = "AutoR3-10"/> However, scientists have not identified the evolutionary pressures that may have caused the spread of these mutations.<ref name = "AutoR3-11"/> This variant of the gene is thought to contribute to increased brain volume<ref>Template:Cite journal</ref> and may correlate with the incidence of tonal languages,<ref name = "AutoR3-9"/> though modern distributions of chromosomes bearing the ancestral forms of MCPH1 and ASPM showed neither microcephalin or ASPM had any significant effect on IQ.<ref name="AutoR3-11"/>
The derived form of MCPH1 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.<ref name = "AutoR3-10"/> While Neanderthals have been suggested as the possible source of this haplotype, the haplotype was not found in the individuals used to prepare the first draft of the Neanderthal genome.<ref name = "Human genome tales"/><ref name = "green"/>
ControversyEdit
The research resultsTemplate:Clarify began to attract considerable controversyTemplate:When in the science world. John Derbyshire wrote that as a result of the findings, "our cherished national dream of a well-mixed and harmonious meritocracy [...] may be unattainable."<ref name = "AutoR3-13"/> Richard Lewontin considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." Bruce Lahn maintains that the science of the studies is sound, and freely admits that a direct link between these particular genes and either cognition or intelligence has not been clearly established. Lahn is now engaging himself with other areas of study.<ref name = "AutoR3-14"/><ref name = "AutoR3-15"/> Later studies have not found those gene variants to be associated with mental ability or cognition.<ref name="AutoR3-16"/><ref name="AutoR3-11"/><ref name="AutoR3-6"/>
Later genetic association studies by Mekel-Bobrov et al. and Evans et al. also reported that the genotype for MCPH1 was under positive selection. An analysis by Timpson et al., found "no meaningful associations with brain size and various cognitive measures".<ref name = "AutoR3-16"/> A later 2010 study by Rimol et al.<ref name="Rimol_2010"/> demonstrated a link between brain size and structure and two microcephaly genes, MCPH1 (only in females) and CDK5RAP2 (only in males). In contrast to previous studies, which only considered small numbers of exonic single nucleotide polymorphisms (SNPs) and did not investigate sex-specific effects, this study used microarray technology to genotype a range of SNPs associated with all four MCPH genes, including upstream and downstream regulatory elements, and allowed for separate effects for males and females.
Other MCPH genesEdit
In addition to MCPH1, other genes have been designated MCPH genes based on their role in brain size. These include WDR62 (MCPH2), CDK5RAP2 (MCPH3), KNL1 (MCPH4), ASPM (MCPH5), CENPJ (MCPH6), STIL (MCPH7), CEP135 (MCPH8), CEP152 (MCPH9), ZNF335 (MCPH10), PHC1 (MCPH11) and CDK6 (MCPH12).<ref>Template:Cite journal</ref>
Research studiesEdit
In March 2019, Chinese scientists reported inserting the human brain-related MCPH1 gene into laboratory rhesus monkeys, resulting in the transgenic monkeys performing better and answering faster on "short-term memory tests involving matching colors and shapes", compared to control non-transgenic monkeys, according to the researchers.<ref name="DSVR-20191229">Template:Cite news</ref><ref name="NSR-20190327">Template:Cite journal</ref>
See alsoEdit
ReferencesEdit
Further readingEdit
External linksEdit
- "Neanderthal Brains"—a lecture by Bruce Lahn from the NYAS podcasts