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- 13 March 2014 11:08 am , Vol. 343 , #6176
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Small Brains Hint at Human History
23 September 2002 (All day)
Big brains gave humans an evolutionary edge, but how did they grow so big? An important clue may come, ironically, from a gene that has been found to stunt the cerebral cortex in people with microcephaly.
A team led by biologist Geoffrey Woods of the University of Leeds, U.K., found the brain-shrinking gene, called ASPM, by sequencing the DNA of people afflicted with primary microcephaly, a familial disease that stunts the growth of the cerebral cortex during development. The researchers discovered that in microcephalic people, chunks of the protein encoded by ASPM are missing because of mutations in the gene. To determine where in the body ASPM is active, they screened different fetal tissues and found the gene expressed in the progenitor cells that produce cerebral cortex neurons.
Previous work with fruit flies suggests how the gene might influence brain size. The fruit fly version of ASPM organizes the spindle fibers that separate chromosome pairs into the two halves of dividing neuronal progenitor cells. The orientation of these fibers determines how many neurons a progenitor cell will produce, and the more neurons produced, the larger the brain. Humans with microcephaly probably have fewer cortical neurons because mutant ASPM disrupts cell division in the progenitor cells, says Christopher Walsh, a neurobiologist at Harvard University and co-author of the new study, which is published online 23 September by Nature Genetics.
However, says Walsh, there are also clues that ASPM is part of a bigger evolutionary story. Searching through genetic databases, the team found similar versions of ASPM in other animals--such as mice and nematode worms--and intriguingly, the ASPM protein was larger in species with proportionally larger brains. Woods believes this suggests that jumps in brain size may have coincided with mutations in ASPM that led to more proliferation among progenitor cells and boosted brain size.
What is exciting about the effect of mutated ASPM, says André Goffinet, a neurobiologist at the University of Namur Medical School, Belgium, is that the brain is only smaller, not more primitive-looking, suggesting that changes in ASPM could indeed have scaled up the human brain during evolution. To test this idea, says Walsh, the team is now trying to move the human ASPM gene into a mouse to see if it will grow a bigger brain.