Saturday, February 25, 2006

Even more brainy genes --- finale


As a finale to the two previous posts about brain evolution, let me end by referring to this study by Mekel-Bobrov et al in Science. If you have followed blogs such as John Hawks, Gene expression or The Scientist you have probably heard about this story before.

The study "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinantin Homo sapiens" has the following abstract:

"The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution."

So the brain has developed significantly during the past 6000 years or so? That is indeed an interestring finding. So what does the ASPM do? What is it related to? Let me recap a brief survey of Hubmed search for "ASPM and brain".
  • It is related to microencephaly and seizures (1)
  • It is also related to cortical malformation (2)
  • The pathological changes are caused by deficient neurogenesis within the neurogenic epithelium (3)
  • It has been strongly positively selected since the divergence from our common ancestor to the chimp (4)
The list goes on and on, but these are maybe the most prevalent reports and topics.

But listen: we're back to discussing brain size again, right? As I claimed in my first brain-evo post "brain size" can mean a lot of things. Since the brain does not evolve like an inflating balloon, it would be much more interesting to know what parts of the brain that increase in size. I'll bet a dollar that we find the prefrontal cortex driving much of this evolution, but that should also mean that the PfC-connected areas would increase in size, too.

I'm diving more into this matter now, and immediately find some interesting and critical remarks by other blogs: again, John Hawks and Gene Expression share their view in the most eloquent way. Read and learn, and don't forget to speculate about what that ASPM haplotype world map actually might mean.

References

(1) ASPM mutations identified in patients with primary microcephaly and seizures. Shen J, Eyaid W, Mochida GH, Al-Moayyad F, Bodell A, Woods CG, Walsh CA. J Med Genet. 2005 Sep ; 42(9): 725-9

(2) Cortical malformation and pediatric epilepsy: a molecular genetic approach. Mochida GH.
J Child Neurol. 2005 Apr ; 20(4): 300-3

(3) Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Woods CG, Bond J, Enard W Am J Hum Genet. 2005 May ; 76(5): 717-28

(4) Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Evans PD, Anderson JR, Vallender EJ, Gilbert SL, Malcom CM, Dorus S, Lahn BT Hum Mol Genet. 2004 Mar 1; 13(5): 489-94

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