The microcephalins (Greek for "small head) are a group of genes associated with brain development.[1][2]Two copies of a loss-of-function mutation in any of the six genes (called MCPH1 to MCPH6) causes primary microcephaly (Online Mendelian Inheritance in Man (OMIM): 251200), a condition characterised by a severely diminished brain.[3][4]
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.[5] 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.[6]
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).[7] 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.[8]
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
^
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)
^
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. PMID12046007. {{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)
^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. PMID17175528.{{cite journal}}: CS1 maint: multiple names: authors list (link)