Human-Neanderthal gene variance is involved in autism

Human-Neanderthal gene variance is involved in autism
The reconstruction of a head of a Neanderthal man, at left, and a Neanderthal skull. One gene identified by UW Medicine and other researchers may be the first identified that distinguishes humans from the Neanderthals. Credit: Wikimedia Commons (Tim Evanson, left photo, and luna04)

A structure that represents the biggest known genetic difference between humans and Neanderthals also predisposes humans to autism.

An international team of researchers led by UW Medicine genome scientist Evan Eichler published the findings today in Nature.

The structure involves a segment of DNA on chromosome 16 that contains 28 . This segment is flanked by blocks of DNA whose sequences repeat over and over.

Such stretches of duplicated DNA, called copy-number variants, are common in the human genome and often contain multiple copies of genes. Although most copy-number variants seem to have no adverse effect on health, some have been linked to disease.

However, when both strands of a segment of DNA are flanked by highly identical sequences, they can be susceptible to large copy-number differences, including deletion, duplication and other changes, during the process of cell division. In this case, deletion, which causes the loss of the segment's 28 genes, results in autism.

In the new study, researchers determined that this structure, located at a region on chromosome 16 designated 16p11.2, first appeared in our ancestral genome about 280,000 years ago, shortly before modern humans, Homo sapiens, emerged. This organization is not seen in any other primate – not chimps, gorillas, orangutans nor the genomes of our closest relatives, the Neanderthals and Denisovans. Yet today, despite the fact that the structure is a relatively new genetic change, it is found in genomes of humans the world over.

Human-Neanderthal gene variance is involved in autism
Forensic reconstruction of a Homo neanderthalensis. Credit: Wikimedia Commons/Cicero Moraes

"Most duplications in our genome are millions of years old, and the speed at which this structure transformed our genome is unprecedented," said co-author Eichler, a professor of genome sciences and an investigator of the Howard Hughes Medical Institute. "The wide and rapid distribution of these copy-number variants suggests the genes within the repetitive sections confer benefit that outweigh the disadvantages that come with the increased risk of autism in some offspring, should deletion occur."

Copy-number variants may play an important role in human evolution because, as a species, we are relatively uniform genetically.

"If you took two chimps out of the wild, they would have twice as many genetic differences in their genomes than you would see between two humans. And orangutans have three times as many differences. Having these structures means we have a way to radically restructure our genome over a very short time frame, bringing about changes that might otherwise take hundreds of millions of years of evolution to acquire – but at the cost of an increased risk of autism and other neuropsychiatric disorders," he said.

One benefit of copy-number variants: They contain multiple copies of genes that can mutate and acquire new, potentially useful functions.

Credit: University of Washington

Of particular interest to the researchers was a gene in the copy-number variants at 16p11.2 called BOLA2, multiple copies of which were found in both flanking regions. The BOLA2 protein in cells appears to form a complex with another protein, called glutaredoxin 3, that allows the cells to capture iron more efficiently and make it available to proteins that require it. This effect appears to be most pronounced early in cell development.

"This ability to help humans to acquire and use this essential element early in life might confer a significant enough benefit to outweigh the risk of having some offspring with autism," Eichler said.

In addition to BOLA2, the mutations within the copy number variant regions appears to have created new protein formed by fusing two regions of the BOLA2 gene with three regions of another gene. This new gene may be the first completely new gene that distinguishes humans from our Neanderthal and ancient hominin cousins, Eichler said. Exactly what role the new protein it creates plays remains unknown. "We're going to work with other research teams to find out what it does but so far we haven't a clue."

Explore further

Gene duplications associated with autism evolved recently in human history

More information: Xander Nuttle et al. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility, Nature (2016). DOI: 10.1038/nature19075
Journal information: Nature

Citation: Human-Neanderthal gene variance is involved in autism (2016, August 4) retrieved 23 July 2019 from
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User comments

Aug 04, 2016
Probably more connections to genetic flaws will be discovered as Rh Neg has been tied to 40,000 y ago when the largest volcanic explosion in the Northern Hemisphere occurred. Then the global Les Chaps magnetic reversal at 41,000 y ago. We are the result.

Aug 04, 2016
Seriously, Editors? You can't size the image in the article without it being cropped on the top and bottom?
Cool pictures, could you please fix the image and remove my complaint?

Aug 04, 2016
@katesisco: References?

- The largest known supervolcano eruption in the last 25 Myrs, and which could have affected hominins, were Lake Toba dated to 69 - 77 kyrs ago. And it didn't affect hominins except locally according to accepted finds. [ https://en.wikipe...ake_Toba ] Those come and go (and in fact it seems no one knows what it is used for), not a very deep change. Or do you imply correlation? But those are gone, see above.

- Volcano eruptions do not cause magnetic reversals, and magnetic reversals do not seem to affect ecology as far as can be seen.

- Rh negative is a blood antigen, and it is likely a membrane transport protein. [Wikipedia] Those come and go, indeed no one seems to know what it is for. So nothing dramatic. Or do you imply correlation? But those are gone, see above.

@NS: You can click such images to pop up uncropped. Most of the times the image text isn't with either, so it is an annoying feature. :-/

Aug 05, 2016
Unlike dogs, where cross-breed breeding enhances health and strength and can help overcome dangerous inter-breeding caused diseases, with humans it seems to be a mistake and/or dangerous.

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