A new study published November 20 in the open-access journal PLOS Biology has identified hundreds of small regions of the genome that appear to be uniquely regulated in human neurons. These regulatory differences distinguish us from other primates, including monkeys and apes, and as neurons are at the core of our unique cognitive abilities, these features may ultimately hold the key to our intellectual prowess (and also to our potential vulnerability to a wide range of 'human-specific' diseases from autism to Alzheimer's).
Exploring which features in the genome separate human neurons from their non-human counterparts has been a challenging task until recently; primate genomes comprise billions of base pairs (the basic building blocks of DNA), and comparisons between the human and chimpanzee genomes alone reveal close to 40 million differences. Most of these are thought to merely reflect random 'genetic drift' during the course of evolution, so the challenge was to identify the small set of changes that have functionally important consequences, as these might help to explain the genomic basis of the emergence of human-specific neuronal function.
The key to the present study, led by Dr Schahram Akbarian of the University of Massachusetts and the Mount Sinai School of Medicine, was not to focus on the "letters" of the DNA code, but rather on what might be called its "font" or "typeface"—the DNA strands of the genome are wrapped in protein to make a chromatin fiber, and the way in which they are wrapped, the "chromatin state", in turn reflects the regulatory state of that region of the genome (e.g. whether a given gene is turned on or off). This is the field that biologists call "epigenetics"—the study of the "epigenome".
Dr Akbarian and colleagues set out to isolate small snippets of chromatin fibers from the frontal cortex, a brain region involved in complex cognitive operations. They were then able to analyze these snippets for the chemical signals (histone methylation) that define the regulatory state (on/off) of the chromatin. The results of their analysis identified hundreds of regions throughout the genome which showed a markedly different chromatin structure in neurons from human children and adults, compared to chimpanzees and macaques.
This treasure trove of short genomic regions is now providing researchers with interesting new leads involving the evolution of the human brain. Although some of the regions have remained unchanged during primate evolution, some more tantalizing ones have recently changed, having a DNA sequence that is unique to humans and our close extinct relatives, the Neanderthals and the Denisovans. The study also uncovered examples where several of these regulatory DNA regions appear to physically interact with each other inside the cell nucleus, despite being separated by hundreds of thousands of base pairs on the linear genome. This phenomenon of "chromatin looping" is implicated in controlling the expression of neighboring genes, including several with a critical role for human brain development.
The study, from laboratories based in the United States, Switzerland and Russia, draws further attention to the role of epigenetics and the epigenome in our biology and our evolution. As Dr Akbarian notes, "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."
Public Library of Science: http://www.plos.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Free-living songbirds show increased stress hormone levels when nesting under white street lights. But different light spectra may have different physiological effects as this study finds, suggesting that using street lights with specific colour spectra may mitigate effects of light pollution on wildlife
Scientists identify the condition aphantasia, in which people cannot create images in their head
The dust in our homes contains an average of 9,000 different types of fungi and bacteria, a study suggests.
A mosquito can bear up to 23 times its total body weight on each leg, which is crucial for landing on water – the insect's secret is way it stands
Tropical species with smaller geographical ranges are more likely to die out in a warming climate than those that can adapt by ‘invading’ new regions
Most people think of bacteria as germs, signs of filth, or unwanted bringers of disease. Slowly, that view …
The gloomy octopuses crowded at Jervis Bay, Australia, appear to spit and throw debris such as shell at each other in what could be an intentional use of weapons
Therapies based on hormones that make us more trusting enhance our natural placebo effect – a finding that could alter the way clinical trials are conducted
The blind, hairless babies born recently at Washington D.C.'s National Zoo are completely dependent on their mothers—who can sometimes accidentally crush them.
The poop-hoarding insects have an amazingly advanced internal GPS that allows them to navigate by day or night.