The evolution of human intellect: Human-specific regulation of neuronal genes
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."
More information: Shulha HP, Crisci JL, Reshetov D, Tushir JS, Cheung I, et al. (2012) Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons. PLoS Biol 10(11): e1001427. doi:10.1371/journal.pbio.1001427
Journal reference: PLoS Biology
Provided by Public Library of Science
- Study characterizes epigenetic signatures of autism in brain tissue Nov 07, 2011 | not rated yet | 0
- Lessons from epigenome evolution: Exploring the epigenome's regulatory function Jun 11, 2012 | not rated yet | 0
- Changes in the path of brain development make human brains unique Dec 06, 2011 | not rated yet | 0
- No evidence for 30-nm chromatin fibers in the mouse genome Oct 04, 2012 | not rated yet | 0
- New study provides mechanistic insights into how gene transcription is regulated in mammalian cells Jul 18, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
Genetics May 24, 2013 | 3 / 5 (2) | 0 |
Can human genes be patented? That was the question posed by Alan J. Snyder, vice president and associate provost for research and graduate studies at Lehigh, and Lee Kaplan, scientific director of cellular and molecular genetics ...
Genetics May 24, 2013 | 4 / 5 (1) | 0
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics May 22, 2013 | 4.5 / 5 (4) | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
16 hours ago | 5 / 5 (2) | 5
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
8 hours ago | not rated yet | 1
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
16 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
16 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
16 hours ago | not rated yet | 0