Uniquely Regulated DNA Strands Could Unlock the Mysteries of Human Intelligence and Disease
Specific, small regions of the human genome that regulate neurons in the brain set us apart from primates.
-- by Heather Kathryn Ross
What makes humans human? Geneticists are teasing out answers to this most complex of questions by studying the “epigenome”—the chemical changes to DNA that regulate which genes will be expressed and how.
According to a new study released this week in the journal PLoS Biology, researchers have identified specific neurons—cells that transmit electrical and chemical signals in the nervous system—that are regulated differently in humans than in our primate and hominid ancestors.
Neurons in the brain allow humans to perform complex cognitive tasks, so this discovery could greatly advance knowledge of human intellect and mental disorders unique to humans, including Alzheimer’s disease and autism.
“Much about human biology and disease cannot be deduced by simply sequencing the genome. Mapping the epigenome of neurons and other cells will help us to better understand the inner workings of our brain, and where we are coming from,” said lead author Dr. Schahram Akbarian of the Mount Sinai School of Medicine in a press release.
Though there are many differences between human DNA and that of a chimpanzee (40 million, to be exact), Akbarian’s team found that only a few (about 470) are functionally relevant and evolutionarily important. Excitingly, they determined that some of these “regulatory DNA regions” have changed relatively recently, and so are unique only to humans and our close ancestors, such as Neanderthals.
“Because some of these sequences…unique to humans are of critical importance for normal brain development, one could speculate that as brains during the course of hominid evolution grew larger and became more complex, these sequences had to adapt as well to ensure normal and healthy brain development,” Akbarian said in an interview with Healthline.
The Expert Take
Strands of human DNA are wrapped in protein to create a “chromatin fiber.” Exactly how they’re wrapped, called their “chromatin state,” determines whether or not the genes they contain are turned “on” or “off,” and so whether they will be expressed or not.
Dr. Akbarian’s team took small chromatin fibers from the frontal cortex of the brain, a region that contributes to attention, memory, planning, initiative, and creativity. They examined the DNA strands for chemical signals, called histone methylation, that determine their chromatin state. The researchers located hundreds of DNA strands that control human brain neurons, whose chromatin structures are very different from those of DNA strands in primate brains.
Incredibly, Akbarian and his colleagues also discovered that that some of these unique DNA strands interact with one another despite being far apart on the human genome. This phenomenon is termed “chromatin looping.”
“Previously, researchers explored DNA sequence differences between humans and non-human primates without paying attention to the fact that the genome inside the cell nucleus is three-dimensionally organized in a non-random fashion (imagine a pasta bowl with the chromosomes…looping around themselves just as long spaghetti does, except in contrast to spaghetti, the chromosomes are, to a certain degree, not randomly arranged),” Akbairan said. “We studied these chromosomal loopings and found several examples where sequences with unique, human-specific chromatin structures were in direct physical contact with each other…bypassing hundreds of thousands of DNA basepairs that separated these sequences on the linear genome. Therefore, to a certain degree, we speculate that there is coordinated evolution and epigenetic regulation of some of the human-specific genes.”
Though these findings may one day help scientists figure out how our brains evolved, why we’re afflicted with mental and developmental disorders, and what role epigenetics plays in making us who we are, answers to these big questions are still years away.
“We hope our findings will provide a treasure trove for researchers interested in identifying DNA sequences, and their epigenetic regulation, that may underlie some of the unique features of the human brain,” Akbarian said. “We also hope identification of human-specific chromatin structures in or nearby disease-associated genes could help form a better understanding of the mechanisms of diseases such as Alzheimer's or schizophrenia.”
Source and Method
Utilizing laboratories in the U.S., Switzerland, and Russia, Akbarian and his team compared the epigenetic profiles of four chimpanzees and three macaques with those of seven human children and four human adults.
University of Southern California researchers provided an overview of epigenetics in a 2004 article in the journal Nature. They explain that epigenetics results in the silencing of specific genes without changes in the actual DNA code. These changes in genetic expression can be passed down from one generation to the next.
Several serious conditions, including cancer and mental retardation, have been linked to changes in epigenetic mechanisms, and researchers are hopeful that advances in “epigenetic therapies” could be used to treat (or even prevent) cancerous tumors.