Well…this may be a little more exciting than the other recent “junk DNA” thread.
“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”, explains Johan Jakobsson, professor of neuroscience at Lund University, who led the study.
Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers 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. 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 two percent of our entire DNA – and examined the proteins themselves to find examples of differences.
The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18 . ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis -acting structural variation establishes a regulatory network that affects human brain evolution.