Health Care

Yale researchers study brain evolution, discover regulatory elements

Recent research, lead by Associate Professor of Genetics, James P. Noonan, along with Steven K. Reilly and Jun Yin, at the Yale University School of Medicine, and recently published in Science, has shed more light on the evolution of the human brain. Thousands of areas in the deoxyribonucleic acid (DNA) that work as regulatory elements, and function similarly to a “dimmer” switch, were functioning at peak capacity within the developing cerebral cortex during human evolution.

These “switches” indicate increased activity in human brains, unlike what was found in mice and rhesus monkeys. It is believed these switches may prompt the expression of genes within the cerebral cortex, which is that part of the brain responsible for language and conscious thinking. There is speculation that this could possibly explain why the human cerebral cortex differs significantly from other mammals.

Noonan and his team zeroed in on multiple biological processes, crucial to human neurological development, that could be linked to the regulatory elements. Another of the team’s accomplishments is the creation of a thoroughly detailed catalogue of the gene regulation changes found in humans. Scientists are quite skilled at identifying the DNA sequence changes that underlie the differences between genomes of various species, and many human genes are similar to those found in other primates, which leads scientists to conclude that, aside from changes within the genes themselves, the manner in which genes are regulated is one of the factors which makes human biology particularly unique.

James P. Noonan

James P. Noonan

Commenting on the team’s discovery, Noonan, who is senior author of the study, said, “Building a more complex cortex likely involves several things, such as making more cells, modifying the functions of cortical areas, and changing the connections neurons make with each other. And the regulatory changes we found in humans are associated with those processes. This likely involves evolutionary modifications to cellular proliferation, cortical patterning, and other developmental processes that are generally well conserved across many species.” Noonan also serves as an investigator with the Kavli Institute for Neuroscience.

It has been difficult to measure these regulatory changes to determine their overall effect, and the task becomes even more daunting when the specific subject is the developing brain, but Noonan and his team at Yale harnessed some new computational and experimental tools to help identify and study the biological effects of those active, regulatory DNA sequences in the human cortex.

The Yale team began by mapping active regulatory elements in the human genome during the first 12 weeks of cortical development. They did so by searching for specific epigenetic changes, which are not brought on by modifications in the DNA sequence. They repeated this mapping in the developing brains of mice and rhesus monkeys before finally comparing the three maps to identify the most active elements in the developing human brain. This lead to the discovery of several thousand regulatory elements showing increased activity in the human brain.

brain map

In order to understand the biological impact of those regulatory changes, the researchers accessed BrainSpan, which is a freely available digital atlas of life long gene expression in the human brain. The data was used to identify groups of genes that exhibited coordinated expression within the cerebral cortex. Afterwards, the regulatory changes they had found were overlaid with these groups of genes, thus allowing them to identify several biological processes associated with a significantly large number of regulatory changes in humans.

Nenad Sestan, a Kavli Institute member, led BrainSpan with assistance from Pasko Rakic, who co-authored the study, and Noonan.

Steven Reilly, first author on the project, said, “While we often think of the human brain as a highly innovative structure, it’s been surprising that so many of these regulatory elements seem to play a role in ancient processes important for building the cortex in all mammals. However, this is often a hallmark of evolution, tinkering with the tools available to produce new features and functions.”

Noonan said that he and his team plan to introduce some of the identified regulatory changes into the mouse genome in order to determine how it will affect the development of a mouse brain.

Previous post

Technological advances in treatment assures improved survival for cancer patients

Next post

Laser cataract surgery - better technology for painless, precise and accurate results

Tracy Venkatesh

Tracy Venkatesh

Tracy Venkatesh has spent twenty years working and interacting with a socioeconomically diverse population in both the private and public sectors, and has held positions in multiple verticals including content development, healthcare, customer relations management, defense and law enforcement.

No Comment

Leave a reply

Your email address will not be published. Required fields are marked *