The Evolution of Human Intellect
A new study 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, as neurons are at the core of our unique cognitive abilities, and may ultimately hold the key to our intellectual prowess
The study was published November 20 in the open-access journal PLOS Biology.
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."
DNA strands are wrapped in protein making up
a chromatin fiber. The way they are wrapped, the
"chromatin state", reflects a regulatory region of the
genome (e.g. whether a particular 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 showing a
markedly different chromatin structure in human
neurons in children and adults, when 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.
"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."
University of Massachusetts
Mount Sinai School of Medicine
Funding: Supported by Yerkes Base Grant, P51RR000165, NEPRC Base Grant P51RR000168, US NIH grants R01MH081943, R21NS076958, R01071476, 1R01NS073947, R01DA021420, R01 AG029360, and Ministry of Education and Science of the RF 16.512.11.2102, 02.740.11.0854; EU FP7 242257-ADAMS; RFBR 11-04-02078. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Citation: 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
Original article: http://www.eurekalert.org/pub_releases/2012-11/plos-teo111512.php