Hidden differences between human and primate brains revealed

January 25, 2016

Researchers at the Hubrecht Institute have used epigenomic analysis of the human and non-human primate brain to identify new genomic elements that specifically changed in the human brain during evolution. These can be employed to investigate how the human brain has developed over time and why, contrary to other primates, it is more susceptible to neurodegenerative diseases as Parkinson’s, Alzheimer’s and ALS. The study is published in Nature Neuroscience this week

The human genome reads 3 billion DNA letters but only 2% of that information is coding for the genes that generate the proteins we are made off. The other 98% contains small regulatory sequences that determine when and how genes are activated. These regulatory sequences function as switches to turn genes on and off. These switches are instructed by epigenetic signatures. Finding these switches in the genome is difficult as the genome is a big place and these switches change dramatically between species while the sequence in genes is overall fairly similar.

The researchers, led by group leader Dr. Menno Creyghton, have now identified were these switches are in the genome using human and non-human primate brain tissue. To do this they have analyzed epigenetic footprints (chemical modifications to the DNA) across the genome, that are selectively present at switches that are turned on. They found thousands of switches that had specifically changed their activity in the human brain compared to other primate species. These regulatory changes likely represent much of the relevant information that makes the human brain different from other primate species.

One of the defining differences between humans and non-human primates is our susceptibility to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and Amyloid Lateral Sclerosis. While some of this specificity is likely due to differences in ageing and environmental factors some of it could also be due to human specific genetic changes in these switches. Finding these will further propel the understanding of the genetic basis for these diseases and lay the groundwork for developing novel therapeutic strategies.