Microcephaly

Microcephaly is a rare condition in which the brain is reduced to about 1/3 its normal volume, with a cranial anatomy reminiscent of early hominids. (Surprisingly, this is associated with only moderate reduction in cognitive ability [Ponting and Jackson 2005]). Six genes are known to cause this condition, and two of these—ASPM and MCPH1—have received the most attention. Loss-of-function alleles at these two genes cause microcephaly when homozygous, and it is thought that alleles of smaller effect at these loci might be responsible for the increased size of the human brain.

This view is supported by the finding that although their amino acid sequence is for the most part highly conserved, both show exceptionally high rates of amino acid substitution in specific regions of the protein, especially in the ancestry of gorillas, chimpanzees, and humans (Zhang 2003; Evans et al. 2004; Kouprina et al. 2004; Wang and Su, 2004; see pp. 532–533 of Evolution for methods for detecting high rates of amino acid substitution). Most strikingly, alleles at each of the two genes have risen to high frequency outside Africa; these are flanked by long regions of low diversity, implying that they have become common within the past few thousand years (Evans et al. 2005; Mekel-Bobrov et al. 2005). (This is the same argument as used in the example of Fig. 15.18.) This rapid increase suggests that these alleles have a selective advantage. However, Currat et al. (2006) show that a population bottleneck, followed by population growth and spread, can also raise neutral haplotypes to high frequency. (See reply by Mekel-Bobrov et al. 2006.)

No association has been found within populations between these alleles and either brain size or IQ (Woods et al. 2006; Mekel-Bobrov et al. 2007; Rushton et al. 2007). Dediu and Ladd (2007) show a correlation across populations between the use of tone in language, and the recently derived ASPM and MCPH1 alleles, but this pattern is hard to interpret, since it is based on comparisons between populations.