Genes and Skull Analysis Reveal the Keys to Our Unique Modern Brains 

A globular brain is a modern one.

A burgeoning body of research suggests that, in many ways, we Homo sapiens are not so different from our close relative Homo neanderthalensis. Like living humans, Neanderthals created art, expressed culture, and cared for members of their community. But we do differ from them in two, possibly connected, ways — the shape of our skulls and the fact that we haven’t gone extinct.

That’s because skulls, crucially, hold brains. Modern human skulls have a round, globular shape, whereas Neanderthals skulls are elongated. In a study released Wednesday in Current Biology, an international team of scientists became the first to identify the genetic factors that likely led to these compelling differences in shape. In turn, they’ve inched us one step closer to an understanding of what it means to be a member of our distinct species.

“The motivation behind studying the unique shape of the human braincase is that it represents one of the most well-established and clearly defined anatomical characteristics that distinguishes Homo sapiens from other human species,” first author and biological anthropologist Philipp Gunz, Ph.D., told Inverse.

Neanderthal brain shape
On the left, the globular endocranial shape of a modern human brian, and on the right the Neanderthal brain shape.

Gunz works as a research fellow at the Max Planck Institute for Evolutionary Anthropology. Skulls, he explains, are windows into brain biology. Scientists have known that Neanderthals and modern humans have skulls of different shapes, but because brain tissue doesn’t fossilize, the underlying biology has remained elusive. So here the team took an interdisciplinary approach, combining fossil skull analysis with brain imaging and modern gene sequencing.

It’s important to note that our brains haven’t always been globular. The oldest Homo sapiens fossils, found in Morocco and dated to around 300,000 years ago, have endocranial volumes that fall in the range of present-day humans, but endocranial shapes that are elongated. That means they had big brains, but not round ones. Previous work conducted by Gunz demonstrates that modern brain size emerged around 300,000 years ago, but globular brains emerged around 40,000 years ago — about the same time the Neanderthals went extinct.

Gunz says that the striking change in Homo sapiens endocranial shapes likely reflects “evolutionary changes in the organization of structures of the human brain, perhaps even in the precise ways that different areas are connected to each other.”

brain
A human brain.

To explore this idea, the team developed an agreed-upon measure of globularity by creating virtual imprints of the interior of the Neanderthal and modern human braincases. They then measured the globularity of the brains of 4,469 living people with the help of MRI brain scans. The scientists also examined the DNA of these participants — searching for fragments of ancient Neanderthal DNA with the hopes that there could be a connection between Neanderthal ancestry and brain shape. Although Neanderthals are extinct, their genetic legacy lives on because of ancient trysts with anatomically modern humans.

The scientists discovered that, although all living humans have skull shapes that are distinctly different from Neanderthal skulls, modern people vary in their degree of brain globularity. Furthermore, they discovered that, among living humans, Neanderthal DNA fragments on chromosomes 1 and 18 are correlated with reduced globularity.

“Like other aspects of brain anatomy, the degree of globularity is likely to be influenced by variation in many different genes, each with a small effect,” Gunz explains. “The effects of each associated Neanderthal fragment were subtle, but detectable due to the use of a large sample size in our study.”

Neanderthal
Virtual reconstruction of a Neanderthal skull.

These Neanderthal fragments were then linked to altered gene activity in brain structure tissues, including the putamen in the basal ganglia and the cerebellum. The genes the fragments associate with, UBR4 and PHLPPI, play an important role in brain development — and it’s likely that here is the link between brain globularity and brain mechanisms. The basal ganglia contributes to cognitive functions like skill learning and planning, and the cerebellum — which contains 50 percent of the brain’s neurons — is important for language processing and working memory.

Gunz emphasizes that the effects of carrying Neanderthal fragments that affect brain shape are subtle at best — and their focus on globularity wasn’t motivated by “the idea that brain shape can tell us something simple about our behavior.” While other scientists have argued that the round, bulging cerebellums of humans may have given us a social and cognitive leg up over Neanderthals, Gunz thinks that “there is no reason to expect any straightforward correlation between overall brain shape and behavior.”

But the findings do suggest that developmental mechanisms likely contributed to the evolution of the modern brain shape and function — allowing us to be the feeling, thinking people we are today. The team plans on continuing to study the genes associated with globularity, with the hope that they will reveal other ways in which that trait is linked to human biology. We’re the only the humans left on Earth — and why is still a mystery.