It has taken us many millions of years to evolve the big, sophisticated brains that we are so proud of. But they're unlikely to be the best we will ever have. New work shows that two genes involved in brain development arose at culturally crucial times during human history and, indeed, might still be evolving.

It makes sense that genes involved in brain morphology, like so many other developmental genes, are subject to natural selection. Bruce Lahn's initial investigation into the subject was reported last year, when he and his colleagues found that two genes that regulate brain size — microcephalin (MCPH1) and abnormal spindle-like microcephaly associated (ASPM) — have been under strong selective pressure in the human evolutionary lineage since we split off from the chimpanzee lineage. Recent work has looked more closely at these two genes to see whether there are signs of more recent selection.

To do this, the distribution of haplotypes for the two genes was studied in a panel of ∼90 cell lines that are representative of human diversity. In both cases, one haplotype stood out as being present in a large proportion of cell lines — a frequency that could not be explained by random or demographic factors and might, therefore, have been driven up in abundance by positive selection. The population distribution of polymorphisms at the two loci and the extent of linkage disequilibrium around each candidate positively selected region support this idea and also point to the occurrence of a recent 'selective sweep' that is still ongoing.

A statistical analysis that is based on estimating the past mutation rate of the genes placed the emergence of the high frequency alleles at ∼37,000 years ago for MCPH1 and ∼5,800 years ago for ASPM. These dates coincide with significant periods in recent human history, the first with the emergence of cultural traits such as music, art and symbolism, and the second with the building of the first cities in Mesopotamia.

The young age of the frequent ASPM variant makes it likely that brain evolution is still continuing. As the authors themselves point out, however, the results should not be overinterpreted. For example, as we cannot tell what force is driving the positive evolution of gene variants, we cannot ascribe it to variation in cognitive function (both genes are also expressed outside the brain). For the same reasons, we should be wary of reading any adaptive significance into the current geographical distribution of MCPH1 and ASPM alleles.