Cerebral Cortex Evolution and the ASPM Gene

Abstract

The cerebral cortex has diversified in many organisms despite having a similar basic plan. Neural cell division at one level and scaling laws at another level can explain interspecies differences in cerebral cortex sizes. Cerebral cortex components are also shaped by adaptive evolution, particularly by ecological and social factors. The genetic basis for brain development has only recently been probed. Guided initially by clinical studies of patients with reduced brain sizes (microcephaly), the gene ASPM has been identified as an important candidate involved in cerebral cortex development. Multiple lines of evidence from evolutionary genetics and functional studies have now implicated the gene in cerebral cortex size evolution across diverse organisms. Given the complexities associated with such a large organ, other genes and their expression patterns as well as noncoding DNA may also play a role in cerebral cortex evolution.

Key concepts:

  • Higher organisms such as mammals and birds show diversity in cerebral cortex size and organization.

  • This diversity is explained partly by neural cell division and scaling laws that constrain the expansion of the cerebral cortex as a function of body size and development.

  • Differences in cerebral cortex organization are also explained by adaptive evolution of animals in their unique niches.

  • Mutations in the gene ASPM cause primary microcephaly or reduced brain size in humans.

  • The gene ASPM controls cortical neurogenesis through cell cycle functions in the brain.

  • There is evidence of accelerated evolution of ASPM in humans and other nonhuman primates with enlarged cerebral cortex sizes.

  • In addition to ASPM, other genes particularly those underlying cellular energetics and regulation of gene expression may be involved in cerebral cortex evolution.

  • The numerous single‐gene, genomic scan and expression studies have its limitations in explaining cerebral cortex evolution.

Keywords: cerebral cortex; ASPM; abnormal spindle‐like; microcephaly associated; microcephaly; molecular evolution

Figure 1.

Diversity in primate neocortex volume (mm3) plotted as a function of body mass (kilograms). Most primates have very small neocortex volumes with humans having the largest neocortex in the primate order. Plotted based on data from Stephan et al..

Figure 2.

The protein structure of ASPM made up of 3 functional domains. * indicates the known mutations that cause primary microcephaly in humans.

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Cox J, Jackson AP, Bond J and Woods CG (2006) What primary microcephaly can tell us about brain growth. Trends in Molecular Medicine 12: 358–366.

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Ali, Farhan(Sep 2009) Cerebral Cortex Evolution and the ASPM Gene. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021765]