Our brain is perhaps the most defining characteristic that sets humans apart from other primates. Its remarkable size, complexity, and abilities far surpass any other species on the planet. Nevertheless, humans have more than 95% of our genetic makeup in common with chimpanzees, our closest living relatives.
Our brain is perhaps the most defining characteristic that sets humans apart from other primates. Its remarkable size, complexity, and abilities far surpass any other species on the planet. Nevertheless, humans have more than 95% of our genetic makeup in common with chimpanzees, our closest living relatives.
Researchers at UC Santa Barbara, including professor Soojin Yi, her doctoral student Dennis Joshy, and collaborator Gabriel Santepere from Hospital del Mar Medical Research Institute in Barcelona, sought to investigate the evolution of genes in various brain cells as compared to those in chimpanzees. They discovered that while our genes code for almost the same proteins as other apes, many of our genes demonstrate significantly higher productivity than those of other primates. Their findings, published in the Proceedings of the National Academy of Sciences, underscore the importance of gene expression in the evolution and functionality of the human brain.
Understanding nature’s instructions
Every gene instructs a cell to produce a specific molecule, but the execution of this instruction doesn’t rely solely on DNA. The information gets transmitted to the cell’s machinery via a molecule known as messenger RNA (mRNA). Researchers evaluate gene expression by measuring the quantity of mRNA produced by a particular gene.
As scientists began to grasp the genome’s function as life’s blueprint, they speculated that the human genome might explain our distinctive characteristics. However, a detailed analysis in 2005 found that humans share approximately 99% of their genes with chimpanzees (a figure that has since been adjusted). This confirmed earlier studies that indicated a minimal genetic difference between humans and chimpanzees.
Now, biologists believe that differences in gene expression may account for these variations. Take the monarch butterfly as an example: the adult butterfly retains the same genome as when it was a caterpillar, but the dramatic differences between these life stages result from gene expression changes. Activating or deactivating certain genes, or varying mRNA production levels, can significantly affect an organism’s traits.
Clarifying the picture
Past studies identified discrepancies in gene expression between humans and chimpanzees, showing that human cells generally exhibit higher levels of gene expression. However, the overall understanding remained vague. The brain contains a multitude of cell types, typically categorized into two primary groups: neurons and glial cells. Neurons transmit electrochemical signals, similar to how copper wires function in buildings, while glial cells perform various other essential tasks, such as insulating the wires, maintaining structural support, and removing waste.
Until recently, research had been limited to bulk tissue samples composed of diverse cell types. However, advancements over the past decade have enabled scientists to analyze individual cell nuclei, allowing for differentiation between cell types and often subtypes.
Yi, Joshy, and Santepere utilized advanced technology that features a narrow channel to isolate each nucleus into separate chambers within an array. They then categorized the cells by type before conducting statistical analysis.
The researchers evaluated gene expression by measuring the amount of mRNA produced by specific genes across humans, chimpanzees, and macaques. An upregulated gene generates more mRNA in one species compared to others, while a downregulated gene produces less. Comparing chimpanzees and humans against macaques allowed the team to identify whether observed differences were due to changes in chimpanzees, in humans, or both.
The authors noted differences in the expression of approximately 5-10% of the 25,000 genes studied. Overall, human cells exhibited more upregulated genes in comparison to chimpanzees, a far larger proportion than what had been observed in previous, less detailed analyses. The percentage increased to 12-15% when they took cell subtypes into account.
“Now we can see that individual cell types have their own evolutionary trajectories, becoming highly specialized,” Yi explained.
Beyond just neurons
The complexity of our neural connections is unmatched in the animal kingdom, but Yi believes our unique intellect derives from more than this aspect alone. Human glial cells make up over half of the cells in our brains, a significantly higher proportion than is found in chimpanzees.
Among glial cells, oligodendrocytes displayed the most pronounced differences in gene expression. These cells produce the myelin sheath that insulates neurons, facilitating quicker and more efficient transmission of their electrical signals. In a collaborative study from the previous year, the team found that humans have a higher ratio of precursor to mature oligodendrocytes compared to chimpanzees. Yi speculates that this could be linked to the remarkable neural plasticity and gradual development of human brains.
“The greater complexity of our neural networks likely didn’t evolve in isolation,” Yi stated. “It couldn’t have come into being without the evolution of these other cell types, which enabled the expansion of neuronal diversity, the total number of neurons, and the intricacy of networks.”
This research focused on cells from a limited number of brain regions, as cells in one area may differ from those in others. Yi plans to investigate the mechanisms behind gene expression variations and how genes relate to distinct traits.
Furthermore, she aims to trace variations in gene expression further back in our evolutionary timeline by examining baselines from even more distantly related species. She’s also interested in exploring genetic differences between modern humans and archaic humans, such as Neanderthals and Denisovans.
Evolution entails more than merely altering genes. “Differential gene expression is truly how the human brain has evolved,” Yi emphasized.
