Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans:

A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolutionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans. Additionally, the lineage from the last human/chimpanzee ancestor to humans shows an excess of nonsynonymous over synonymous substitutions, which is a signature of positive Darwinian selection. A comparison of polymorphism and divergence using the McDonald-Kreitman test confirms that ASPM has indeed experienced intense positive selection during recent human evolution. This test also reveals that, on average, ASPM fixed one advantageous amino acid change in every 300,000-400,000 years since the human lineage diverged from chimpanzees. We therefore conclude that ASPM underwent strong adaptive evolution in the descent of Homo sapiens, which is consistent with its putative role in the evolutionary enlargement of the human brain.

This doesn't seem to be a gene that led to the "Great Leap" about 40,000 years ago-but something that might be a candidate for the more gradual increase in brain capacity among hominids over the past 2 million years.

godless comments:

An important thing to note is that the gene associated with a highly abnormal phenotype (microcephaly) also had variants that produced natural phenotypic variation, because without phenotypic variation there could have been no natural selection. One should keep this in mind when some disingenuously claim that there is a stark distinction between those genes implicated in mental retardation and those involved in normal variation. The two sets have highly nontrivial overlap.

Update II (from Razib): Future Pundit comments.