Reason for bigger brain in humans

Transgenic mouse embryo with human HARE5 showing increased brain size Image modified from:
Transgenic mouse embryo with human HARE5 showing increased brain size
Image modified from:

Humans have evolved as the most intelligent species during the course of evolution with incredible thought process, imagination and unique capabilities to use abstract language and do complex math. Also the size of human brain has increased dramatically from the ancient pre historic Homo sapiens to the modern Hi-tech man. However other animals including the closest relatives of man- chimpanzees and monkeys have not shown considerable progress during the course of evolution. What could be the reason for this rapid development of human brain unlike chimpanzee?

Several studies aimed at the genes, that are differentially present or expressed between the humans and chimpanzee to understand the facts underlying the uniqueness. However, a research team led by Dr. Debra Silver studied this issue from a different angle and found out that specific regions on the genome or DNA are the reason for bigger brain and intelligence in humans. It’s a well known fact that DNA or genetic material contains genes which are transcribed in to RNA that in turn forms proteins by translation. The transcription of these genes is regulated by specific DNA sequences called enhancers. Mining of genomic data base from humans and chimpanzees allowed the scientists to identify six such enhancers that regulate the expression of genes responsible for brain development. These regulatory enhancers are named (human accelerated regulatory enhancers) HARE1 through HARE6.

“I think we’ve just scratched the surface, in terms of what we can gain from this sort of study,” said Debra Silver, an assistant professor of molecular genetics and microbiology in the Duke University Medical School. “There are some other really compelling candidates that we found that may also lead us to a better understanding of the uniqueness of the human brain.”

Furthermore, HARE5 was found to be present near Frizzled8 gene responsible for brain development and disease. To understand the role and importance of HARE5, researchers used transgenic mouse embryos having Frizzled8 gene under the control of human or chimpanzee HARE5 enhancer. Surprisingly embryos with human HARE5 enhancer developed a bigger brain compared to chimpanzee HARE5. Also the human HARE5 enhancer showed a higher activity and was active much earlier to that of chimpanzee enhancer, leading to the increased proliferation and differentiation of neural progenitor cells in to neurons.

“What’s really exciting about this was that the activity differences were detected at a critical time in brain development: when neural progenitor cells are proliferating and expanding in number, just prior to producing neurons,” Silver said. “Human HARE5 mice had brains 12% larger in area compared with chimpanzee HARE5 mice. The neocortex, involved in higher-level function such as language and reasoning, was the region of the brain affected. Producing a short list of strong candidates was in itself a feat, accomplished by applying the right filters to analysis of human chimpanzee genomes,” said co-author Gregory Wray, professor of biology and director of the Duke Center for Genomic and Computational Biology.

This study was published in renowned journal Current Biology. The research team is looking forward to study the role of HARE5 enhancer in mice up to adulthood, which will give more insights in to brain development and brain-related diseases like Alzheimer’s.


The original publication can be accessed here.