Humans and chimpanzees share a common ancestor, but 4 to 6 million years ago they split off on different evolutionary paths. Chimps continued to walk on all fours and live in trees, while we lost our fur and grew past the need for a tail. But it was our large brains that set us the most apart from our closest relatives. The human brain (about the size of 10 tennis balls) is three times bigger than a chimp’s.
There are multiple theories for why we evolved large and complex brains. Some evolutionary biologists think humans developed bigger bodies as a response to environmental pressures such as living in open, unforested habitats that required more cooperation and thinking to catch prey. Others speculate our brains needed to grow to handle the information needed to manage social relationships. And in a new study published in Science today, geneticists offer a third explanation: We just got lucky.
Lead author Katie Pollard, the director of the Gladstone Institute of Data Science and Biotechnology in California, likes to think of it as rolling dice. Every time another member of a species is born, there’s a chance that mutations will spring up in their genome. Each new generation gets more opportunities to score big with tweaks in the gene pool that increase the odds of survival. These beneficial mutations are more likely to stick around as organisms thrive and pass them on to offspring. In the case of humans and brain size, eventually, the buildup of mutations would be reflected in changes in the overall genome, Pollard says.
These random mutations could have contributed to the 49 short DNA sequences in our genome called human accelerated regions (HARs). Pollard and her team were the first to find these segments back in 2006 when comparing the genomes of humans to chimpanzees. HARs work as gene enhancers, controlling which genes are turned up or down during embryonic development, especially for brain formation.
HARs in humans are very similar in each individual but vary when compared to accelerated regions in other vertebrates like chimps, frogs, and chickens. Since the initial discovery, research has found a connection between HARs and multiple traits that make our species distinct. And while Pollard has spent a lot of time understanding how HARs helped humans evolve, the current study focuses on why HARs emerged in the first place.
The team collected data from 241 mammalian genomes (in concert with the larger Zoonomia project) and identified 312 accelerated regions across all of them. Most of the accelerated regions identified acted as neurodevelopmental enhancers, indicating a connection to brain development. But when comparing human and chimp DNA sequences, 30 percent of HARs were in areas of the genome where the DNA was folded differently. This suggests the structural variations in the human genome likely came from a random mutation during reproduction. “Mutations happen all the time and everytime sperm and eggs get made, there are some mistakes that cause cuts, deletions, and other edits to the DNA,” explains Pollard. “Many of the mutations don’t make any difference, but now and then some have a positive effect and that’s actually very rare.”
In this case, scrunching and folding up DNA in different ways seemed to help with fitting a copy of the genome in every cell of the body. “It’s a big surprise that genome folding is involved since it hadn’t been on anyone’s radar when studying human accelerated regions,” says Pollard. “We had been thinking of DNA as a text file in a big folder full of A, C, T, and G’s, and looking for patterns as you move linearly through the sequence.”
The folding change would have affected how enhancers regulated gene activity in early humans. Depending on how the DNA was folded, enhancers could have been situated near new sequences, giving them different genes to target and boost. In humans, it just so happened that most of the adjacent genes were involved in brain development. In other words, we won the mutation lottery.
“The main achievement of this study is the discovery that the evolutionary history of HARs is connected in some way with the complex dynamics of structural configurations of the human genome,” says Anastasia Levchenko, a genetic researcher for the Institute of Translational Biomedicine at Saint Petersburg State University in Russia who has previously studied HARs’s role in brain development. However, she would like to see more research on the sequence of events in the evolution of the human genome. For example, it’s possible that HARs appeared way earlier than the changes in our DNA folds, or that DNA folding is only one factor contributing to the creation of HARs.
What’s more, humans might have used other genetic pathways to develop different features from other animals. Pollard’s study is one of 11 papers published in Science today as part of the Zoonomia Project, an international collaboration that aims to understand the codes behind shared and specialized traits across hundreds of mammalian species. For example, Zoonomia researchers identified the distinct parts of Balto’s genome that helped the sled dog deliver a serum to a remote Alaskan village, as well as genetic variants in early humans that could play a role in modern-day diseases. Another paper focuses on using information from DNA to predict which species are more likely to face extinction. All together, identifying the different genomes will open the door to understanding mammalian evolution and what exactly makes us uniquely human.