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 facilitated cognitive advances that helped define what it means to be human.

These genes, found only in people, appeared between three and four million years ago, just prior to a period when the fossil record demonstrates a dramatic brain enlargement in ancestral species in the human lineage, researchers said on Thursday.

The three nearly identical genes, as well as a fourth nonfunctional one, are called NOTCH2NL genes, arising from a gene family dating back 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 Université Libre de Bruxelles and VIB/KULeuven in Belgium.

"It is the ultimate evolutionary question and it is thrilling to work in this area of research," added biomolecular engineer David Haussler, scientific director of the University of California, Santa Cruz Genomics Institute and a Howard Hughes Medical Institute investigator.

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

"It would be great if we could sequence Lucy’s genome," said UC-Santa Cruz biomolecular engineering research scientist Sofie Salama, while noting the improbability of doing that.

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

NOTCH2NL gene abnormalities were found to be linked to neurological conditions including autism, schizophrenia and both abnormally large and abnormally small head size.

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