DNA in Your Brain Could Reveal What Makes You Human

Apes and humans are extremely similar genetically, so what makes us so different in real life?

Certain regions of DNA in our brain could be responsible for what distinguishes us from apes (Credit: Penn Today)

The human race is, in my eyes, fascinating. Our species, Homo sapiens, descended from primates, yet we have evolved so much. It begs the question: what makes us so different from our close relatives, the apes?

At first glance, the solution seems simple. Just compare the DNA sequences of humans and apes and observe where we diverged, right? Wrong. We share over 99% of our DNA with chimpanzees, one of our closest relatives, and among the differences that do exist, many of them may have no effect on making us human. This problem has led scientists to support an alternate hypothesis: what makes us human isn’t simply our gene sequence, but how we regulate which ones are expressed.

DNA (light blue + gray helix) has transcription factors (proteins that regulate genes) attached to it (Credit: News Medical)

Not all of the genes encoded in our DNA are expressed, so if humans and apes share almost all of their DNA, then maybe how our genes are regulated (i.e. when, where, and how strongly genes are expressed) is what sets us apart. This is where it gets tricky. It’s been an ongoing challenge for researchers to find the exact location of ‘gene dimmers’, or regulatory elements that have been positively selected throughout the evolution of mankind.

‘Positive selection’ is an extremely important part of this challenge. Elements that have been positively selected are things that started as a genetic mutation but eventually became standard in a population as organisms with the mutation survived and reproduced more often. Gene dimmers that have been positively selected are the ones that researchers want to study.

As humans evolved, certain gene dimmers were positively selected (Credit: YourGenome.org)

For years, scientists who wanted to study the relationship between humans and apes have had a list of challenges (like the ones above) but no solution. That is, until now.

Researchers at the Swiss Institute of Bioinformatics (SIB) and the University of Lausanne, both located in Lausanne, Switzerland, have come up with a new way of identifying large regions of these positively selected gene regulators in the brain. Jialin Liu, the lead author of this study, says,

“We show for the first time that the human brain has experienced a particularly high level of positive selection, as compared to the stomach or heart for instance. This is exciting, because we now have a way to identify genomic regions that might have contributed to the evolution of our cognitive abilities!”

Let’s look at what they did and why we should care.

What They Did

The group of researchers’ new method of finding gene regulatory regions in the brain uses a machine learning model, specifically a support vector machine (SVM) for those interested. To train the ML model, the researchers provided experimental data on how strongly different transcription factors (proteins involved in gene regulation) bind to their corresponding regions of DNA in different tissues from around the body. This data was gathered using a technique called ChIP-sequencing, which lets us observe the interactions between protein and DNA. After training the model, they performed the following three steps to infer positive selection:

1. Inferring the DNA sequence of the ancestor species of an organism using its DNA (from the tissue).
2. Calculating the change in a transcription factor’s binding due to DNA changes between the input organism’s species and its inferred ancestor.
3. Determining if the difference (from the above step) is significant enough to be due to positive selection.

Diagram of the steps that the researchers’ model takes to infer positive selection (Credit: Jialin Liu et al.)

With this model, the scientists were able to perform evolutionary comparisons between humans, chimpanzees, and gorillas. Additionally, as Marc Robinson-Rechavi, a group leader at SIB and study co-author, says:

“We now know which are the positively selected regions controlling gene expression in the human brain. And the more we learn about the genes they are controlling, the more complete our understanding of cognition and evolution, and the more scope there will be to act on that understanding.”

This research supports previous research regarding what makes humans so different from genetically similar species. An important discovery in human biology was made by Katherine Pollard and her co-researchers in 2006, when they discovered a small stretch of 118 nucleotide bases that became known as human accelerated region 1 (HAR1). After lots of research, scientists found that HAR1 evolved extremely slowly in organisms other than humans, which could be why we are so different. Additionally, HAR1 was found to encode a completely new type of RNA, which could have contributed to making us unique.

This brings us to an incredibly important question: why should we care? Well, what these researchers have done lets scientists finally observe differences in gene regulation between humans and related species. This means that we can finally discover the true answer to what makes us so different. It’s obvious that our brains are different, as we have much bigger brains than chimpanzees, but the underlying genetic and evolutionary reasons are yet to be completely understood. Additionally, it may help us improve our understanding of evolution as a whole.

To me, biology is such an exciting field because we never know what we’ll discover next, whether it be about our tiny cells to the evolution of our species! As technology gets better, scientific research will get easier and faster, but we will never know everything there is to know about the mystery that is life. I look forward to seeing future research regarding this novel tool, as the researchers have stated that “[their] method can still be improved”, but for now, let’s continue to look to the future of research!

Want to learn more? Check out the official research paper for this study here:

Robust inference of positive selection on regulatory sequences in the human brain