From: Andy Soos, ENN
Published May 7, 2012 12:54 PM

The Development of the Human Brain

A brain-development gene found exclusively in humans has an unusual evolutionary history and could contribute to what makes us distinctly human. Equally surprising, this is a partial gene created from an incomplete duplication of its parent gene in the prehistoric human genome. The incomplete duplication of the gene may account for its behavior. This may have been some ancient error which was reproduced successfully. Deoxyribonucleic acid (DNA) is a nucleic acid containing the genetic instructions used in the development and functioning of living organisms. The DNA segments carrying this genetic information are called genes. Likewise, other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.


Gene duplication is an important driving force in creating physical changes in living things during evolution, explained the researchers studying the SRGAP2 gene family. The paper is published in the May 4 advanced online edition of Cell. It is one of a pair of papers on this gene.

The human (Homo sapiens) genome is stored on 23 chromosome pairs and in the small mitochondrial DNA. Twenty-two of the 23 chromosomes belong to autosomal chromosome pairs, while the remaining pair is sex determinative. The haploid human genome occupies a total of just over three billion DNA base pairs.

"Our data point to a mechanism," Dennis (one of the authors)explained, "for the partial gene interfering with the function of its ancestral gene." Instead of taking a while to settle, this mutation started working, according to Dennis, “immediately at its birth some 2 million to 3 million years ago.

The timing of the duplication coincides with evolutionary changes in the brain anatomy in species of the genus Homo. The partial gene also was discovered in the genomes of the Neanderthals and Denisovans, who bore remarkable resemblance to humans. The gene duplicates are not found in chimpanzees, gorillas, orangutans or in the genomes of any other mammalian species.

The period of this partial duplication even corresponds to the transition of the slender, upright African pre-human primate genus, Australopithecus, to the larger-brained genus, Homo.

"While the appearance of this mutation during that era of primate evolution is exciting, we should be careful to avoid implying cause-and-effect relationships," Dennis cautioned. Many other human-specific gene mutations, environmental conditions, social interactions and other contributing factors were at play.

Scientists from several fields, including embryology and the neurosciences, are interested in how this human specific gene mutation works. Using mice, researchers previously showed that the SRGAP2 gene has a role in fetal development of the cortex, where thought, spatial reasoning and other higher brain activities reside.

The May 4 accompanying paper in Cell by Polleux’s group indicates that the duplicate gene plays a role in shaping the cortex by working in concert with its parent gene to regulate the migration of brain cells and the formation of brain cell surface structures, such as branches, knobs and connective outgrowths.

Eichler and his group began studying the evolutionary history of this gene family, located on Chromosome 1, after analysis of hundreds of human genomes revealed that sequence information for SRGAP2 was incorrect or missing. The gene had been misassembled and duplicate copies were not sequenced or characterized. This is not uncommon for genes that are difficult to analyze with standard methods, especially those genes embedded within parts of our genomes holding multiple copies that are nearly identical.

Eichler and his team decided to complete the missing data with genetic information from a human hydatidiform mole, a rare product of the fertilization of an empty egg by a sperm. Because the collection of cells that make up the mole has but half of each pair of human chromosomes, geneticists refer to it as haploid.

"The data we leveraged from the haploid mole allowed us to reconstruct the complex evolutionary history of the SRGAP2 gene family since about 6 million years ago when humans diverged from non-human primates," the researchers reported.

By identifying nearly identical sequences not recorded in the reference human genome, the researchers confirmed that the SRGAP2 gene had duplicated three times. Although many mammals have the gene, the segmental duplications occurred exclusively in humans. The promoter and a few other parts of the gene were first duplicated about 3.4 million years ago.

Unlike many of the mutations that created the approximately two-dozen human-specific genes discovered so far, the partial gene is no longer located in an area of change. Perhaps, the researchers surmise, it was transported to a more stable location during the second duplication event, or the product became indispensable to human adaptation and evolution. The relocation permitted it to function over the long haul.

"This gene is among the most fixed of human-specific genes," Dennis said. "There’s almost no variation in the number of copies from one human genome to another. Just about everyone has two copies, she explained, which is unusual for such a recently duplicated gene segment."

Evidence for the role of this gene family in human brain development and intellectual capacity comes from the Eichler group’s study of mutations in children with developmental delays, certain types of epilepsy, and brain malformations.

This long ago accidental change or mutation may have caused major long term consequences in the development of intelligence.

For further information Evolution or DNA

Evolution Chart by image via University of Washington

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