In the genome of Homo sapiens, about 98% of DNA sequences are non-coding regions that were previously disregarded as ‘junk DNA.’ In fact, junk DNA contains a variety of regions which precisely control the expression of genes. Now, a team of stem cell researchers at Lund University has examined what it is in our DNA that makes human and chimpanzee brains different and found that the answer lies in non-coding DNA.
Johansson et al. identify a transcription factor called ZNF558 that is expressed in human but not chimpanzee forebrain neural progenitor cells. Image credit: Lisichik.
“Instead of studying living humans and chimpanzees, we used stem cells grown in a lab,” said senior author Professor Johan Jakobsson, a neuroscientist in the Department of Experimental Medical Science at the Wallenberg Neuroscience Center and Lund Stem Cell Center at Lund University.
“The stem cells were reprogrammed from skin cells. Then we examined the stem cells that we had developed into brain cells.”
Using the stem cells, Professor Jakobsson and colleagues specifically grew brain cells from humans and chimpanzees and compared the two cell types.
They then found that humans and chimpanzees use a part of their DNA in different ways, which appears to play a considerable role in the development of our brains.
“The part of our DNA identified as different was unexpected,” Professor Jakobsson said.
“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.”
“Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are — which only makes up about 2% of our entire DNA — and examined the proteins themselves to find examples of differences.”
“The new findings indicate that the differences appear to lie outside the protein-coding genes.”
“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 per cent 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%, which appears to be important. This is a surprising finding.”
The authors believe that in the future their new results may also contribute to genetically-based answers to questions about psychiatric disorders such as schizophrenia.
“But there is a long way to go before we reach that point, as instead of carrying out further research on the two per cent of coded DNA, we may now be forced to delve deeper into all 100% — a considerably more complicated task for research,” Professor Jakobsson said.
The findings appear in the journal Cell Stem Cell.
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Pia A. Johansson et al. A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development. Cell Stem Cell, published online October 7, 2021; doi: 10.1016/j.stem.2021.09.008
