Big brain evolution: causative genes found (Evolution)

by David Turell @, Thursday, May 31, 2018, 23:20 (880 days ago) @ David Turell

It looks as if they appeared and activated 3 million years ago:

"A set of three nearly identical genes found only in humans appear to play a critical role in the development of our large brains, according to a study led by researchers at the University of California, Santa Cruz.

"The genes appeared between 3 and 4 million years ago, just before the period when fossils show a dramatic increase in the brain sizes of human ancestors. In modern humans, the genes are involved in genetic defects associated with neurological disorders.

"They belong to an ancient family of genes known as Notch genes, first discovered in fruit flies and named for a genetic defect causing notched wings.

"'This is a family of genes that goes back hundreds of millions of years in evolutionary history and is known to play important roles in embryonic development. To find that humans have a new member of this family that is involved in brain development is extremely exciting," said senior author David Haussler,


"The new human-specific Notch genes were derived from NOTCH2, one of four previously known mammalian Notch genes, through a duplication event that inserted an extra partial copy of NOTCH2 into the genome. This happened in an ancient ape species that was a common ancestor of humans, chimpanzees, and gorillas. The partial duplicate was a nonfunctional "pseudogene," versions of which are still found in chimp and gorilla genomes. In the human lineage, however, this pseudogene was "revived" when additional NOTCH2 DNA was copied into its place, creating a functional gene. This new gene was then duplicated several more times, resulting in four related genes, called NOTCH2NL genes, found only in humans.

"One of the four NOTCH2NL genes appears to be a nonfunctional pseudogene, but the other three (NOTCH2NLA, NOTCH2NLB, and NOTCH2NLC) are active genes that direct the production of truncated versions of the original NOTCH2 protein. Notch proteins are involved in signaling between and within cells. In many cases, the Notch signaling pathway regulates the differentiation of stem cells in developing organs throughout the body, telling stem cells when to become, for example, mature heart cells or neurons.


"The NOTCH2NL genes are especially active in the pool of neural stem cells thought to generate most of the cortical neurons. By delaying their maturation, the genes allow a larger pool of these stem cells (called "radial glia") to build up in the developing brain, ultimately leading to a larger number of mature neurons in the neocortex (the outer layer of the brain in mammals; in humans, it hosts higher cognitive functions such as language and reasoning).

"This delayed development of cortical neurons fits a pattern of delayed maturation characteristic of human development, Haussler said. "One of our most distinguishing features is larger brains and delayed brain development, and now we're seeing molecular mechanisms supporting this evolutionary trend even at a very early stage of brain development," he said.


"A major part of the research involved careful and precise sequencing of the region of chromosome 1 where the NOTCH2NL genes are located in 8 normal individuals and 6 patients with 1q21.1 deletion/duplication syndrome. (The researchers also analyzed the genomes of three archaic humans, two Neanderthals, and one Denisovan, finding in all of them the same three active NOTCH2NL genes that are present in modern humans.)

"The sequencing results showed that the NOTCH2NL genes are variable in modern humans. The researchers identified eight different versions of NOTCH2NL, and Haussler said there are probably more. Each version has a slightly different DNA sequence, but it remains unclear what effects these differences may have.


"Other genes involved in human brain development seem to have arisen through a duplication process similar to the creation of NOTCH2NL. A notable example is the gene SRGAP2C, which is thought to increase the number of connections between neurons. Locations in the genome where such duplications and rearrangements occur repeatedly, known as "duplication hubs," make up about 5 percent of the human genome and seem to have been important in human evolution, Haussler said."

Comment: the bigger size requires a bigger skull and a differently shaped female pelvis, and those new genes are unknown so far. Did this occur by chance or by design?

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