From genes to genius: What makes the human brain unique?

Our brain is the organ that most distinguishes us from other primates. Its large size, complexity and capabilities exceed those of any other species on our planet.

However, we share up to 95% of our genome with chimpanzees, our closest living relatives. So how can such closely related species – at the genomic level – exhibit such stark differences in brain function? 

It turns out, certain brain cell types may hold the key, according to a study led by Professor Soojin Yi at the University of California, Santa Barbara. The research was conducted with collaborators at the Hospital del Mar Medical Research Institute in Barcelona.

The findings show that while humans and chimpanzees share many of the same genes, alterations in gene activity may account for distinctive features of the human brain.

Shifting the focus to gene expression

Researchers have long known that genes serve as a blueprint for an organism, but actual biological processes hinge on how, when, and to what extent these genes are turned on or off. 

Scientists quantify this by measuring messenger RNA (mRNA), the molecule that relays a gene’s instructions to cellular machinery. 

As they compared the human genome to that of chimpanzees, scholars once believed the differences resided in the genes themselves. 

However, with well over 90% genetic similarity, that explanation alone appeared insufficient. Instead, gene expression – the amount of mRNA produced – seems to be the crucial factor in explaining why the human brain diverges so markedly from primate relatives.

Gene expression and brain evolution

There is growing evidence that even tiny alterations in how genes are regulated can lead to significant changes in anatomy and behavior. “Differential gene expression is really how human brains evolved,” Yi said.

The researchers set out to identify precisely which genes in specific types of brain cells might exhibit notable differences in expression among humans, chimpanzees, and other primates.

Until recently, scientists typically studied gene expression by taking tissue samples that contained mixtures of cell types. This approach made it difficult to pinpoint the unique activity patterns within different classes of brain cells. 

In the new study, the team tackled this challenge by using modern techniques capable of analyzing single-cell nuclei. By isolating and sequencing the genetic content of individual brain cells, the researchers could categorize them according to cell type before measuring gene expression levels.

Varying cell types among primates 

This focus on specific cell populations yielded a wealth of detail about how gene activity in individual regions and cell types varies among primates. 

Data from humans, chimpanzees, and macaques revealed that many genes exhibit shared expression patterns, but humans often display enhanced expression. 

Certain cell types, such as those linked to vital cognitive processes, show particularly strong upregulation in humans when compared to other primates.

Glial cells and brain expansion

Neurons attract much of the attention in discussions of the human brain’s capabilities. But the study highlights that glial cells – non-neuronal cells that provide structural support, insulation, and other vital functions – may also play a critical part in distinguishing the human brain from its primate cousins. 

Human brains generally have a higher ratio of glial cells to neurons than chimpanzee brains, hinting at how these support cells could contribute to advanced cognitive abilities.

One especially noteworthy subset of glia, known as oligodendrocytes, appears to demonstrate significant differences in gene expression. These cells form myelin sheaths that protect neurons and speed up the transmission of signals. 

The researchers discovered that humans maintain a higher proportion of precursor oligodendrocytes than chimpanzees do, a difference that may underlie extended development times and heightened plasticity in the human brain.

Future research directions

Though the study examined only certain brain regions, its insights suggest that gene expression in additional areas of the brain might also differ substantially among primates. 

Yi and her collaborators plan to investigate these questions and delve into the molecular mechanisms that power these evolutionary shifts. 

The experts also intend to explore more distantly related species to reconstruct the broader evolutionary history and to assess how archaic humans, such as Neanderthals and Denisovans, fit into the narrative.

In the larger context, gene expression research holds promise for explaining how relatively minor genomic differences yield large functional disparities. It shows that evolution can occur via subtle adjustments in the regulation of existing genes rather than the wholesale creation of new genes. 

By refining our understanding of these regulatory networks in the brain, scientists are one step closer to explaining how humans achieved their exceptional cognitive abilities.

The study is published in the journal Proceedings of the National Academy of Sciences,

Image Credit: Matt Perko

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