Three genes give evolutionary insights into human brain size

Scientists have found a set of genes that may explain the unusually large size of the human brain in comparison with other apes.

The same genes – which are specific to humans and contribute to the production of brain cells - may also make humans more susceptible to autism and schizophrenia.

'It's fascinating to think that the same mechanism that helped enable a bigger brain might also make us susceptible to these disorders,' said Dr Sofie Salama at the University of California, Santa Cruz. 'We're paying the price for the gain we got in our evolution.'

The team led by Professor David Haussler at Santa Cruz, used laboratory-grown brain organoids to look for genes that are expressed differently in humans and apes.

They pinpointed three genes which were missing in the closest human relatives, chimpanzees and gorillas. These genes, of NOTCH2NL family, direct the developing brain to create more neurons, as shown in a companion study led by researchers at the Free University of Brussels, Belgium, published in Cell.

Professor Haussler's team looked at the NOTCH2NL-related DNA in the different species and concluded that an ancestral type of the gene, NOTCH2, got duplicated by mistake in the common ancestor of all great apes.

This copied version was non-functional until around 3.5 million years ago when the original NOTCH2 gene partly overwrote the broken copy and made it functional. This is around the time when the brain size of early humans began to expand. This new active gene, the NOTCH2NL, duplicated twice more, resulting in the three genes described in the study.

The genes are found in the region implicated in abnormal brain size. Deletions in this region are linked to microcephaly (abnormally small brain), while duplications can lead to macrocephaly (abnormally large brain). These genes are also implicated in autism and schizophrenia.

The genes are present in our recent early human relatives, the Neanderthals and Denisovans, but not in other apes. This fits very well with the differences in brain size and cognitive power between our and other genetically close species.

Further studies may reveal the exact contribution to brain development; the genes come in eight slightly different iterations, and it is unclear how these contribute to individual differences.

'Understanding the key to our greater cognitive abilities is a huge opportunity of our time,' said Professor Haussler.