Another difference from the monkey
The human and chimpanzee brains differ in non-coding regulatory DNA
Marina Astvatsaturyan, Echo of Moscow
Cell biologists from Lund University in Sweden, studying the role of non-coding parts of the genome, which used to be called non-functional "junk" DNA, found that humans and chimpanzees use part of such DNA in different ways. According to scientists, this had a decisive impact on the development of a unique human brain. Chimpanzees are our closest living relatives. Despite the significant similarity of our protein-coding genes, the human forebrain is larger and more complex than that of chimpanzees.
"Previously, scientists were looking for the reason for this in the part of DNA that is responsible for the production of proteins and tried to find examples of differences between humans and chimpanzees in the proteins themselves," says the head of the new study, Professor Johan Jakobsson of Lund University, in a press release What makes us human? The answer may be found in overlooked DNA.
Jacobson and colleagues discovered a new factor (ZNF558) that regulates transcription, the process of reading information from DNA, and found out that it is active in the precursor cells of human forebrain neurons, but not in chimpanzees. This factor arose about 100 million years ago to regulate the activity of a family of mobile genetic elements, but now it regulates the gene (SPATA18), which in turn regulates the degradation of important cellular structures of mitochondria.
And the activity of the identified transcription factor ZNF558 itself is regulated by the length of the non-coding DNA element, which is called a tandem repeat with a variable number. In chimpanzees, it turned out to be longer than in humans.
The results of the study are published in the journal Cell Stem Cell (Johansson et al., A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development), and they give a mechanistic idea of how structural variations in DNA create a regulatory network that affects the evolution of the human brain. Jacobson is confident that this idea will help to get genetically based answers to questions about the nature of mental illnesses, such as schizophrenia, which occur only in humans.
The authors have shown that the role of the identified transcription factor in maintaining normal mitochondrial function. In experiments on brain organoids, they found that with an inactive factor, human organoids are smaller in size in the early stages of development, and in the later stages there are more mature neurons in them.
From this, the authors concluded that the transcription factor is important for the coordinated development of brain elements in the early stages of its growth. Organoids were of two types, they were grown from stem cells obtained by reprogramming human and monkey skin cells.
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