Regulatory network impacting brain evolution found in “junk DNA,” says study

Human DNA has a close resemblance to that of the chimpanzee, which in evolutionary terms is the closest living relative of humans. Stem cell scientists from the Lund University in Sweden recently identified an earlier overlooked part of human DNA, known as non-coded DNA.

Regulatory network impacting brain evolution found in “junk DNA,” says study
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This part seems to contribute to a variation which, in spite of all the similarities, might detail why human brains work differently. The research has been published in the Cell Stem Cell journal.

The closest living relative in evolutionary terms to humans is the chimpanzee and studies imply that human kinship descends from a common ancestor. Around five to six million years ago, the evolutionary paths divided resulting in the chimpanzee of today, and Homo Sapiens, humankind in the 21st century.

In recent research, stem cell scientists from Lund analyzed what is in human DNA that makes it different from the brain of a chimpanzee—and the researchers discovered the answers.

Instead of studying living humans and chimpanzees, we used stem cells grown in a lab. The stem cells were reprogrammed from skin cells by our partners in Germany, the USA, and Japan. Then we examined the stem cells that we had developed into brain cells.”

Johan Jakobsson, Professor, Neuroscience, Lund University

Jakobsson headed the research.

The scientists employed stem cells—they particularly cultured brain cells from humans and chimpanzees and matched the two cell types. The scientists identified that humans and chimpanzees use a part of their DNA in separate ways, which seems to play a vital role in the development of human brains.

The part of our DNA identified as different was unexpected. It was a so-called structural variant of DNA that were previously called ‘junk DNA’, a long repetitive DNA string which has long been deemed to have no function.”

Johan Jakobsson, Professor, Neuroscience, Lund University

Jakobsson also adds, “Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are—which only makes up about two percent of our entire DNA—and examined the proteins themselves to find examples of differences.”

The recent observations thus show that the differences seem to be present outside the protein-coding genes in the “junk DNA”—which constitutes most of human DNA and is thought to have no function.

This suggests that the basis for the human brain’s evolution are genetic mechanisms that are probably a lot more complex than previously thought, as it was supposed that the answer was in those two percent of the genetic DNA. Our results indicate that what has been significant for the brain’s development is instead perhaps hidden in the overlooked 98 percent, which appears to be important. This is a surprising finding.”

Johan Jakobsson, Professor, Neuroscience, Lund University

The stem cell technique employed by scientists from Lund is revolutionary and hence allowed this kind of research. The technique was acknowledged by the 2012 Nobel Prize in Physiology or Medicine.

Japanese scientist Shinya Yamanaka identified that specialized cells can be reprogrammed and advanced into all kinds of body tissue, and Lund researchers transformed them into brain cells. This technique enabled the analysis of the differences between humans and chimpanzees employing ethically defensible methods.

Why did the researchers want to investigate the difference between humans and chimpanzees?

Jakobsson also states, “I believe that the brain is the key to understanding what it is that makes humans human. How did it come about that humans can use their brain in such a way that they can build societies, educate their children and develop advanced technology? It is fascinating!”

Jakobsson presumes that the current observations might also contribute to genetically based answers to questions on psychiatric disorders, like schizophrenia—a disorder that is unique to humans—in the future.

But there is a long way to go before we reach that point, as instead of carrying out further research on the two percent of coded DNA, we may now be forced to delve deeper into all 100 percent—a considerably more complicated task for research,” added Jakobsson.

Source:
Journal reference:

Johansson, P. A., et al. (2021) A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development. Cell Stem Cell. doi.org/10.1016/j.stem.2021.09.008.

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