Science Article

Our braininess is one of our species' defining features. With a volume of 1200 to 1500 cubic centimetres, our brains are three times the size of those of our nearest relative, the chimpanzee. This expansion may have involved a kind of snowball effect, in which initial mutations caused changes that were not only beneficial in themselves but also allowed subsequent mutations that enhanced the brain still further. "You have some changes and that opens opportunities for new changes that can help," says John Hawks at the University of Wisconsin-Madison.

In comparison to that of a chimp, the human brain has a hugely expanded cortex, the folded outermost layer that is home to our most sophisticated mental processes, such as planning, reasoning and language abilities. One approach to finding the genes involved in brain expansion has been to investigate the causes of primary microcephaly, a condition in which babies are born with a brain one-third of the normal size, with the cortex particularly undersized. People with microcephaly are usually cognitively impaired to varying degrees.

Genetic studies of families affected by primary microcephaly have so far turned up seven genes that can cause the condition when mutated. Intriguingly, all seven play a role in cell division, the process by which immature neurons multiply in the fetal brain, before migrating to their final location. In theory, if a single mutation popped up that caused immature neurons to undergo just one extra cycle of cell division, that could double the final size of the cortex.

Take the gene ASPM, short for "abnormal spindle-like microcephaly-associated". It encodes a protein found in immature neurons that is part of the spindle - a molecular scaffold that shares out the chromosomes during cell division. We know this gene was undergoing major changes just as our ancestors' brains were rapidly expanding. When the human ASPM sequence was compared with that of seven primates and six other mammals, it showed several hallmarks of rapid evolution since our ancestors split from chimpanzees (Human Molecular Genetics, vol 13, p 489).

Other insights come from comparing the human and chimp genomes to pin down which regions have been evolving the fastest. This process has highlighted a region called HAR1, short for human accelerated region-1, which is 118 DNA base pairs long (Nature, vol 443, p 167). We do not yet know what HAR1 does, but we do know that it is switched on in the fetal brain between 7 and 19 weeks of gestation, in the cells that go on to form the cortex. "It's all very tantalising," says Katherine Pollard, a biostatistician at The Gladstone Institutes in San Francisco, who led the work.

Equally promising is the discovery of two duplications of a gene called SRGAP2, which affect the brain's development in the womb in two ways: the migration of neurons from their site of production to their final location is accelerated, and the neurons extrude more spines, which allow neural connections to form (Cell, vol 149, p 192). According to Evan Eichler, a geneticist at the University of Washington in Seattle who was involved in the discovery, those changes "could have allowed for radical changes in brain function".