- A new study concludes that the speed at which the human brain evolved may help explain why our species experiences autism.
- According to the authors, certain genes associated with autism are downregulated in humans compared with other species.
- They argue that autism in humans may be a byproduct of the rapid evolution of human cognitive traits.
Although we humans like to think of ourselves as the pinnacle of evolution, that does the rest of the natural world a serious injustice. Humans cannot spin webs, fly, breathe underwater, produce venom, or swing through the trees.
However, we certainly do have a uniquely powerful and intricate brain. Complex language, in-depth forward planning, deep empathy, and vibrant culture are just some of the feats that this powerful organ has enabled.
Our neurological capabilities undoubtedly imparted evolutionary benefits to our ancient ancestors. They allowed us to spread throughout the world and adapt to all the environments that Earth has to offer.
According to the authors of a new study, however, the dizzyingly complex circuitry of our brains — and the speed at which some of it evolved — may also be the reason why autism is common in our species.
Using single-cell RNA-sequencing, scientists have now shown that, in the mouse brain, there are at least 49 cell types.
Perhaps surprisingly, the human brain has no brain cell types that are specific to only us. We use the same collection of cell types as a rodent.
This, as the authors of the new study infer, means that the incredible difference between human and other minds cannot be due to specialized cells.
Rather, it is due to the ways in which they are connected and the levels of gene expression within each cell.
Scientists have long noted that some proteins evolve and change much more quickly than others. Certain proteins in mice, for instance, are almost identical to proteins found in the human body. Others, however, are so different that they barely seem related at all.
Scientists have conducted studies to understand what factors influence whether a protein is conserved over millennia or quickly altered as species evolve.
These studies suggest that the greatest influence on the rate of change is how prevalent that protein is in the body: If a protein is expressed in large amounts throughout the whole body, it is unlikely to change quickly. This is because any modifications to it are likely to upset a pathway or function somewhere in the body.
On the other hand, proteins that are relatively rare in the body have a little more freedom: If they change, even if the outcome is negative, they will tend to have less impact on the whole organism. This gives them more room for evolutionary maneuvering.
The authors of the recent study wondered whether this same rule might also be true for cell types.
Could it be that the rarest brain cell types have the most freedom to evolve, and that in our case, this freedom resulted in our outsized cognitive prowess? And could this help explain brain changes related to ASD?
In agreement with the authors’ hypothesis, previous research showed that certain genes involved in autism susceptibility are often found in so-called human-accelerated regions (HARs) of the genome.
HARs are sections of the genome that are well conserved in other mammals but evolved relatively rapidly in humans. This swift evolution implies that they might be involved in some of the traits that make humans different.
This might mean that, at some point between now and our last shared ancestor with chimpanzees, we developed some neuronal changes specific to our cognitive ability that also increase the likelihood of autism.
The scientists involved in this study theorize that that might be the case. So, they set out to test that hypothesis. As mentioned before, the brain cell types in mice and humans are identical. However, the gene expression within each type of cell differs.
In other words, even though a mouse and a human cell might look the same and do a similar job, when you look at how active individual genes are, you can find significant differences. So, this is where they focused their efforts.
In agreement with their hunch, the scientists found that the more abundant a cell type was, the more similar its gene expression was across six mammalian species. Conversely, rarer cell types showed large differences in gene expression between the six species.
Additionally, the authors write that “L2/3 IT neurons evolved unexpectedly quickly in the human lineage compared to other apes.” They also noted a disproportionate down-regulation of genes associated with autism.
Medical News Today reached out to Luke Barr, MD, a board-certified neurologist and Chief Medical Officer at SensIQ, who was not involved in the study. He explained the importance of these particular neurons, saying that:
“Layer 2/3 intratelencephalic excitatory neurons are critical for higher-order cortical processing. They form long-range connections across different regions of the cortex, essentially integrating information and supporting complex cognition, such as abstract reasoning, social cognition, and language.”
Research suggests that these communication pathways are particularly important in cognitive skills that are specific to humans.
Importantly, Barr also told us that, because of their role in linking distributed brain regions, problems in their development or the way in which they work, “could have significant downstream effects on how the brain coordinates information, which may relate to [autism].”
Overall, the study authors believe that as the human brain rapidly evolved, it caused changes that made autism more likely to occur.
Barr commented on these conclusions, noting that “the idea that [autism] may represent an evolutionary trade-off is provocative.”
“While speculative, this is consistent with a long-standing hypothesis in neuroscience: That the very features which make human cognition extraordinary — such as enhanced connectivity and cortical expansion — may also introduce vulnerabilities,” he told us.
Barr was careful to remind us that correlation is not the same as causation, and that “this work remains more theoretical than clinically actionable at this stage.” However, he remained hopeful for the future.
“By focusing on how these specialized neurons develop, communicate, and adapt in both typical and atypical brains, we may uncover new mechanisms of [autism].”
“This could eventually inform targeted interventions,” Barr told MNT, “whether pharmacologic or behavioral, that support connectivity and functional integration in the cortex.”
Overall, this study adds to the growing body of evidence suggesting that, rather than a disorder, autism is a “neurodevelopmental variation that may be linked to the very neural systems that enable uniquely human cognitive abilities,” Barr concluded.
MNT also spoke with John Jay Gargus, MD, PhD, a professor of medical genetics and genomics, pediatrics, and physiology and biophysics, at the University of California, Irvine.
Gargus, who was not involved in the study, has conducted research on the role of mitochondria in autism.
Mitochondria are often referred to as the powerhouses of the cell. Present in nearly all cell types, they produce adenosine triphosphate (ATP), the energy currency of the cell.
Commenting on the recent study, Gargus told MNT that: “The observations are useful but are simply an elaboration of data already out in a variety of genome-wide association studies (GWAS), and most significantly, they lack an underlying hypothesis of why these evolutionary changes have occurred.”
Gargus believes that the researchers did not account for the importance of energy production. Our brain makes up just 2% of our body weight, but uses up around 20% of our energy.
A rapidly expanding brain during evolution would have caused a huge increase in energy demands, which Gargus believes provides insights into autism.
In his view, autism “reflects a mismatch between the evolutionary demands of our modern brains and the metabolic systems that support them.”
Rather than autism being caused by evolution, Gargus believes that because our brains are so energy-hungry, disturbances during childhood — for instance, even minor mitochondrial issues — could “tip the scale toward developmental conditions like [autism].”
This is clearly a complex topic, and no doubt researchers will continue to investigate well into the future. Casting a scientific lens far back into our evolutionary history is certainly a challenging endeavour.
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