Howard Hughes Medical Institute researchers have identified a gene that appears to have played a role in the expansion of the human brain’s cerebral cortex.

By comparing the gene’s sequence in a range of primates, including humans, as well as non-primate mammals, the scientists found evidence that the pressure of natural selection accelerated changes in the gene, particularly in the primate lineage leading to humans.

The researchers, led by Howard Hughes Medical Institute (HHMI) investigator Bruce Lahn at the University of Chicago, focused on a gene called the Abnormal Spindle-Like Microcephaly Associated (ASPM) gene. Loss of function of the ASPM gene is linked to human microcephaly, a severe reduction in the size of the cerebral cortex.

For each species, the researchers identified changes in the ASPM gene that altered the structure of the resulting protein, as well as those that did not affect protein structure. Only those genetic changes that alter protein structure are likely to be subject to evolutionary pressure, Lahn said. Changes in the gene that do not alter the protein indicate the overall mutation rate – the background of random mutations from which evolutionary changes arise. Thus, the ratio of the two types of changes gives a measure of the evolution of the gene under the pressure of natural selection.

Lahn and his colleagues found that the ASPM gene showed clear evidence of changes accelerated by evolutionary pressure in the lineage leading to humans, and the acceleration is most prominent in recent human evolution after humans parted way from chimpanzees.

According to Lahn, among the next steps in his research will be to understand how ASPM functions in the brain. Studies hint that the protein produced by the gene might regulate the number of neurons produced by cell division in the cerebral cortex.

Howard Hughes Medical Institute