Thursday, September 08, 2005

This is Bruce Lahn's brain on ASPM and MCPH1   posted by Razib @ 9/08/2005 02:30:00 PM

Researchers Say Human Brain Is Still Evolving. The crest of articles already seems enormous on Google News as I write. The papers are in the current issue of Science. I gotta run, but I assume other people on this blog will have comments, so I figured I'd act as the thin edge of the wedge....


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

Patrick D. Evans,1,2 Sandra L. Gilbert,1 Nitzan Mekel-Bobrov,1,2 Eric J. Vallender,1,2 Jeffrey R. Anderson,1 Leila M. Vaez-Azizi,1 Sarah A. Tishkoff,4 Richard R. Hudson,3 Bruce T. Lahn1* 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 adaptively in anatomically modern humans suggests the ongoing evolutionary plasticity of the human brain. It also makes Microcephalin an attractive candidate locus for studying the genetics of human variation in brain-related phenotypes.


Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens

Nitzan Mekel-Bobrov,1,2 Sandra L. Gilbert,1 Patrick D. Evans,1,2 Eric J. Vallender,1,2 Jeffrey R. Anderson,1 Richard R. Hudson,3 Sarah A. Tishkoff,4 Bruce T. Lahn1* 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.

Addendum, Rikurzhen:

Q: are there phenotypes (e.g. brain size or IQ) associated with these alleles?
A: no, these alleles have not been tested; but loss of function alleles of these genes affect brain size

Also note that there are almost certainly hundreds of QTLs for IQ, and previous attempts to find linkage or assocation have been not especially fruitful -- largely because of low statistical power. However, because there is such a strong selective signature on these alleles, there is likely to be a pheotypic effect, albeit likely a small one. From the Microcephalin paper:

The specific function of Microcephalin in brain development makes it likely that selection has operated on the brain. Yet, it remains formally possible that an unrecognized function of Microcephalin outside of the brain is actually the substrate of selection. If selection indeed acted on a brain-related phenotype, there could be several possibilities, including brain size, cognition, personality, motor control, or susceptibility to neurological and/or psychiatric diseases. We hypothesize that D and non-D haplotypes have different effects on the proliferation of neural progenitor cells, which in turn leads to different phenotypic outcomes of the brain visible to selection.

Jason M. adds: The files have been added to the GNXP files section. Not to be missed! Also here's my thread over on MetaFilter.

Update from Razib: Of course you should read what John Hawks has to say. Andrew advises caution. Slasdhot has a thread (I don't see anything below a mod score of 4 but there still isn't much to see...though John popped up in there). Here is a technorati query you might want to keep track of.

TangoMan adds: Maps below the fold.

Click on maps for the larger versions.