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. Hence, it has been assumed that variants have a role in brain development. 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. 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. 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 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. However, scientists have not identified the evolutionary pressures that may have caused the spread of these mutations. This variant of the gene is thought to contribute to increased brain volume and may correlate with the incidence of tonal languages, though modern distributions of chromosomes bearing the ancestral forms of MCPH1 and ASPM showed neither microcephalin or ASPM had any significant effect on IQ. 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. 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 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." Bruce Lahn