Microcephalin

Microcephalin (MCPH1) is one of six genes causing primary microcephaly 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. Hence it has been assumed that variants have a role in brain development, but in normal individuals no effect on mental ability, brain size or behavior has been attributed to either this or another similarly studied microcephaly gene, ASPM.

Structure
Microcephalin proteins contain the following three domains:
 * N-terminal BRCT domain
 * Central microcephalin protein domain
 * C-terminal BRCT domain

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 (any time between 14,000 and 60,000 years ago) and has spread to become the most common form throughout the world except Sub-Saharan Africa; this rapid spread suggests a selective sweep. However, scientists have not identified the evolutionary pressures that may have caused the spread of these mutations. Modern distributions of chromosomes bearing the ancestral forms of MCPH1 and ASPM are correlated with the incidence of tonal languages, but the nature of this relationship is far from clear.

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. 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.

Controversy
The research results began to attract considerable controversy in the science world. John Derbyshire, writing in 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." Richard Lewontin considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." Lahn maintains that the science of the studies are sound, and freely admits that a direct link between these particular genes and either cognition or intelligence has not been clearly established. Bruce Lahn is now engaging himself with other areas of study.

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., however, found "no meaningful associations with brain size and various cognitive measures".

Family members
In addition to MCPH1. the other five family members are:

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.)