Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans

@article{Evans2005MicrocephalinAG,
  title={Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans},
  author={Patrick Evans and Sandra L. Gilbert and Nitzan Mekel-Bobrov and Eric J. Vallender and Jeffrey R. Anderson and Leila M. Vaez-Azizi and Sarah A. Tishkoff and Richard R. Hudson and Bruce T. Lahn},
  journal={Science},
  year={2005},
  volume={309},
  pages={1717 - 1720}
}
The gene Microcephalin (MCPH1) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage. We show that one genetic variant of Microcephalin in modern humans, which arose ∼37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift. This indicates that it has spread under strong positive selection, although the exact nature of the selection is unknown. The finding that an important brain gene has continued to evolve… 
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410 Citations

Comment on "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens" and "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans"

It is shown that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

The overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ, and highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.

Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

Extensive evidence for positive selection having acted on the majority of microcephaly loci not just in primates but also across non-primate mammals is found, suggesting that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals.

Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ.

Cytoskeletal genes regulating brain size.

Normal variants of Microcephalin and ASPM do not account for brain size variability.

No evidence that the selected alleles were associated with increases or decreases in brain volume is found, which suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.

MCPH , a disorder of neurogenic mitosis affecting foetal brain growth

One of the most notable trends in human evolution is the dramatic increase in brain size that has occurred in the great ape clade, culminating in humans, which is believed to have resulted in the authors' ability to perform higher cognitive functions.

Response to Comment on "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens" and "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans"

Computer simulations are presented to argue that the haplotype structure found at the microcephalin and ASPM genes can be better explained by demographic history rather than by selection.

Primary microcephaly: do all roads lead to Rome?

Molecular evolutionary analysis of human primary microcephaly genes

It can be inferred that protein-coding sequence of MCPH genes might not be the sole determinant of increase in relative brain size during primate evolutionary history.
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References

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Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids,…

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