Hey, a kind reader took pity on my lack of access to the latest issue of Human Molecular Genetics and sent me a pdf of the article. This is wonderful! I don't even have to get off my butt and walk over to the library, or log in for online access—I just whine a little on the weblog, and presto, someone sends me a present!^*

Anyway, I've now read through Evans et al. (2004), and it's fairly interesting. It's a comparison of ASPM sequences from common chimpanzee (Pan troglodytes), lowland gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), white-handed gibbon (Hylobates lar), crab-eating macaque (Macaca fascicularis), black-and-white colobus monkey (Colobus guereza), owl monkey (Aotus spp), Bolivian squirrel monkey (Saimiri boliviensis), domestic cat (Felis cattus), domestic dog (Canis familiaris), cow (Bos taurus), and sheep (Ovis aries). Whew. What they mainly describe are the K_a/K_s ratios in the ASPM gene in these various lineages. K_s is the frequency of synonymous changes in the gene; that is, changes in the DNA sequence that don't actually cause any amino acid changes in the ASPM protein. K_a is the frequency of nonsynonymous substitutions in the gene, that is, changes in the DNA that actually lead to changes in the protein. A high K_a/K_s ratio means that there have been a greater number of amino acid substitutions in the lineage than we would expect by chance alone, and is evidence that there has been selection for the changes. The question is whether the hominid lineage has experienced more selection for changes in this gene involved in brain size than have other mammalian lineages.

The answer seems to be yes. Here is figure 1 from the paper; remember that greater K_a/K_s values indicate greater selection on ASPM in the indicated lineage.

Phylogeny of ASPM in primates. The great ape lineages are highlighted in red, and the ape lineages leading to humans in bold. The K_a/K_s ratios of individual segments of the phylogenetic tree are indicated.

The authors' conclusions:

These observations indicate that the elevated rate of ASPM protein evolution is a distinct feature of the ape lineages leading to humans, and is not found in either non-hominoid primates or other non-primate mammalian orders examined. We therefore conclude that the evolution of ASPM is significantly and uniquely accelerated in the descent of Homo sapiens relative to other mammalian lineages.

A few other tidbits:

• I mentioned before that the gene has these interesting calmodulin-binding repeats, the IQ repeats, and that the number of repeats is roughly correlated with the size of the nervous system on a very broad phylogenetic scale. This doesn't hold up very well with the mammals—we humans have the same number of IQ repeats as cats and cows. We do have more than mice, but rodents seem to be unusual within the mammals in this regard.
• They estimate that positive selection began operating on ASPM 18 million years ago. We aren't entirely the result of an abrupt shift in just our hominid ancestors, but the result of a very long-term selective process that has also been at work on our primate cousins.
• They estimate that "15 of the 19 nonsynonymous substitutions that occurred between the last human/chimpanzee ancestor and humans may have been adaptive and driven to fixation by positive selection."
• There is a statistically significant greater frequency of nonsynonymous change in the IQ domains and a microtubule-binding domain than in other parts of the protein.

The evidence is good that evolution has been selectively tweaking this one gene known to affect our brain size. Now if only we knew exactly what effect these little ASPM changes have on the brain...

^*Although one must wonder if this is the path down which teenage girls with webcams have also gone. Will I sink to begging for lab supplies on the ol' blog? "I'll keep my clothes on for a box of micropipette tips, a microgram of DiI, and some kimwipes..."

Evans PD, Anderson JR, Vallender EJ, Gilbert SL, Malcom CM, Dorus S, and Lahn BT (2004) Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human Molecular Genetics Advance Access published January 13, 2004.