Genetic clues to how humans got big brains

Scientists are a step closer to learning how the human brain evolved after pinpointing genes thought to be responsible for its dramatic increase in size.

Scientists have pinpointed three genes that may have played a pivotal role in an important milestone in human evolution: the striking increase in brain size that aided cognitive advances that helped define what it means to be human.

These genes, found only in people, appeared between three million and four million years ago, just before when the fossil record demonstrates a dramatic brain enlargement in ancestral species in the human lineage, researchers say.

The three nearly identical genes, as well as a fourth non-functional one, are called NOTCH2NL genes, arising from a gene family dating hundreds of millions of years and heavily involved in embryonic development.

The NOTCH2NL genes are particularly active in the reservoir of neural stem cells of the cerebral cortex, the brain's outer layer responsible for the highest mental functions such as cognition, language, memory, reasoning and consciousness.

The genes were found to delay development of cortical stem cells into neurons in the embryo, leading to the production of a higher number of mature nerve cells in this brain region.

"The cerebral cortex defines to a large extent what we are as a species and who we are as individuals. Understanding how it emerged in evolution is a fascinating question, touching at the basic origins of mankind," said developmental neurobiologist Pierre Vanderhaeghen of Universite Libre de Bruxelles and VIB/KULeuven in Belgium.

The species Australopithecus afarensis, which combined ape-like and human-like traits and included the well-known fossil dubbed "Lucy", lived in Africa about the time these genes are estimated to have appeared.

The genes are absent in people's closest genetic relatives. None were found in monkeys or orangutans.

A non-functional cousin of these genes was detected in gorillas and chimpanzees.

But the researchers found the genes in two extinct species in the human lineage, Neanderthals and Denisovans.

The findings on the NOTCH2NL genes were detailed in two studies published in the journal Cell.