University of California, Santa Barbara’s Professor Soojin Yi and colleagues aimed to determine how genes in different types of brain cells have evolved compared to those in chimpanzees. They found that, while our genes code for almost all the same proteins as other apes, many of our genes are much more productive than those of other primates.
Differential gene expression in the human brain compared to nonhuman primate brains is a key molecular feature of human evolution. Joshy et al. show that differential gene expression of human brains encompasses highly divergent sets of cell-type-specific changes. Despite such cellular diversity, human brain cells have experienced a general increase of gene expression rather than a decrease of gene expression. The authors reveal specific functional programs that have experienced differential expression in different cell types and genomic and epigenomic features that correlate with such changes.
As scientists began to understand the role of the genome as life’s blueprint, they thought perhaps the human genome could explain our unique traits.
But a thorough comparison with chimpanzees in 2005 revealed we share 99% of our genes — though scientists have since revised this number.
This confirmed earlier studies based on small numbers of genes that had suggested there was only a small difference between the human and chimpanzee genome.
Now biologists suspect that gene expression may underlie these differences. Consider a monarch butterfly. The adult has the same genome as when it was a caterpillar. The incredible differences between the two life stages all come down to gene expression. Turning on and off different genes, or having them code for more or less mRNA, can drastically alter an organism’s traits.
Getting Clearer Picture
Previous research has found differences in gene expression between humans and chimpanzees, and that human cells tend to have higher gene expression, but the picture was blurry.
The brain is made up of many varieties of cells.
Traditionally, scientists organized brain cells into two major types: neurons and glial cells.
Neurons carry electrochemical signals, a bit like the copper wiring in a building.
Glial cells perform most of the other functions, such as insulating the wires, supporting the structure and clearing out debris.
Until recently, scientists could only study bulk tissue samples composed of many different types of cells. But within the past decade, it’s become possible to assay cell nuclei one at a time.
This allows researchers to distinguish between cell types, and often even subtypes.
Professor Yi and co-authors used datasets generated from a device with a very narrow channel to separate each nucleus into its own chamber in an array.
Then they grouped the cells by type before performing statistical analysis
They measured gene expression by observing the amount of mRNA a specific gene produced in humans, chimpanzees and macaques.
An upregulated gene produces more mRNA in a given species compared to the others, while a downregulated gene produces less.
Comparing chimpanzees and humans to macaques enabled the researchers to tell when differences between the two apes were due to changes in chimpanzees, changes in humans, or both.
The authors recorded differences in the expression of about 5-10% of the 25,000 genes in the study.
In general, human cells had more upregulated genes compared to chimpanzees.
This is a much larger percentage than researchers found when they couldn’t break down the analysis by cell type. And the percentage grew to 12-15% when the authors began to consider cell subtypes.
“Now we can see that individual cell types have their own evolutionary path, becoming really specialized,” Professor Yi said.
Not Just Neurons
The intricacy of our neural pathways is unrivaled in the animal kingdom. However, the researchers suspect that our unique intellect isn’t a result of this on its own.
Human glial cells account for more than half of the cells in our brains, a much larger percentage than in even chimpanzees.
Among glial cells, oligodendrocytes showed the greatest differences in gene expression. These cells create the insulation that coats neurons, enabling their electrical signals to travel much more quickly and efficiently.
In a collaborative study published the previous year, the scientists observed that humans have a higher ratio of precursor versus mature oligodendrocytes compared with chimpanzees.
They suspect this may relate to the amazing neural plasticity and slow development of human brains.
“The increased complexity of our neural network probably didn’t evolve alone,” Professor Yi said.
“It could not come to existence unless all these other cell types also evolved and enabled the expansion of the neuron diversity, the number of neurons and the complexity of the networks.”
The findings were published in the Proceedings of the National Academy of Sciences.
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Dennis Joshy et al. 2024. Accelerated cell-type-specific regulatory evolution of the human brain. PNAS 121 (52): e2411918121; doi: 10.1073/pnas.2411918121
This article was adapted from an original release by the University of California, Santa Barbara.