Autism spectrum disorder (ASD) is a worldly health problem that is one of the most complicated neurodevelopment disorders in science. However, what in case, a part of its prevalence is not based on disease, but on evolution itself?
Stanford University released a groundbreaking study in 2025 in Molecular Biology and Evolution in which they suggest just that.
The study presents a general law of neuronal evolution in that most neurons develop gradually within a severe natural selection, but a single group of neurons in the human brain has developed disproportionately. The researchers believe that this accelerated evolution process might be one of the factors that lead to the high rates of autism within humans nowadays.
The Brain Building Blocks Under Evolutionary Pressure.
The brain has thousands of types of neurons that have their functions and genetic identity. Alexander L. Starr and Hunter B. Fraser and their Stanford team studied more than one million neurons in various species of mammals to study the evolution of these cell types.
Most significantly, they discovered the following rule: the more prevalent a type of neuron is, the slower its evolution. This is understandable, there is no need to have an entire brain-wide mutation which may disrupt essential processes so natural selection keeps it in effect. On the other hand, the freedom of evolution is greater in rare types of neurons.
This trend is similar to that already noted by geneticists on a molecular scale: proteins whose expression is high change more slowly than those with lower expression. The paper unites molecular evolution to cell type evolution and demonstrates that this principle extends across the full spectrum, all the way to neural circuits.
The Layer 2/3 Intratelencephalic (IT) Neurons Outlier.
There was one neuron type that bucked this trend totally, layer 2/3 intratelencephalic (L2/3 IT) neurons, which are crucial to the communication between brain parts and higher thought.
These neurons have developed at a remarkably rapid pace in humans as compared to other apes such as chimpanzees and gorillas. The researchers found this based on mass single-nucleus RNA sequencing of many brain regions such as the medial temporal gyrus (MTG) and the prefrontal cortex, which are essential in memory, language as well as social behavior.
What was even more astonishing was that they evolved: L2/3 IT neurons in humans were subjected to drastic gene silencing associated with autism suggesting that natural selection supported the lower expression of these genes with time.
Evolutionary Trade offs: Adaptation as a Side Effect.
Why should the human brain deactivate genes associated with autism? It can be found in the repetitive trade-offs of evolution. Starr and Fraser claim that positive selection, which is evolution favoring any advantageous trait, could have motivated gene expression changes to promote human thought, communication or adaptability.
Nevertheless, the same genetic changes can have sensitised our brains to developmental imbalances which in turn further predisposes one to develop autism. Differently put, the same genes which are the source of our humanity can be used as the source of our weakness.
This idea is consistent with earlier hypotheses that uniquely human traits language, social reasoning and creativity) were developed by the rapid rewiring of the cortex, which also exposured them to the risk of developing neurodevelopmental conditions.
Changes in Gene Expression and Human Specific.
In human beings, the research determined that in L2/3 IT neurons, autism related genes like DLG4 (PSD-95) are expressed at considerably lower levels compared to chimpanzees or macaques.
DLG4 is critical in the strength and plasticity of synapses the capacity of brain connections to change with experience.
Suppressed activity of these genes may have precision tuned neural functioning or energy expenditures in the developing human brain. However, the flip side of this reduction is that, even minor genetic or environmental disturbances can push them past the ASD expression threshold to result in the autism-like behavior of a person.
The researchers refer to it as a tipping-point model, i.e. where positive evolutionary adaptations led to the human brain approaching a balancing point between neurodevelopmental susceptibility and optimal cognitive flexibility.
Genetic and Organoid Study Evidence.
To determine if these differences in gene expression were actually genetic (and not merely environmental), the team utilized the hybrid organoids, or small models of the brain that are grown in a laboratory using both human and chimpanzee cells.
When the two genomes were compared in the same laboratory conditions, human alleles were found to have lower expression of genes related to autism. This eliminated environmental effects and gave solid support to polygenic positive selection evolution that favors co ordinated changes in large numbers of genes.
The researchers concluded that natural selection in early humans had an organized down-streaming of the activity of dozens of autism-related genes, which was probably due to its role in improving brain developmental processes that are critically important to the survival of our species.
The Evolutionary Edge and Its Costs.
Evolution tends to enhance one aspect at the expense of another. The genetic adaptations that might have enhanced language, imagination, and extended planning, in this instance, also contributed to the possibility of neurological disequilibrium.
This evolutionary paradox does not stem out of autism itself. The paper compares the research to schizophrenia another social cognition disorder, which has also been associated with human specific brain circuits.
Both of these states may be the price of complexity, as a by-product of our fast-paced cerebral development.
Another New Framework of Evolution of the Human Brain.
The Stanford experiment proves a general principle of evolution of neurons:
The common types of neurons are evolving slowly because of strong constraint except when they are positively selected in the human lineage.
This understanding redefines the thinking of scientists regarding the origins of human intelligence and neurodiversity. According to it, genetic mistakes are not all that accumulates to give birth to autism, but rather adaptive processes that gave our species its peculiarity of the brain structure.
Why It Matters
Knowledge about the evolutionary history of autism would revolutionize the studies and perception by the community. It points out that autism characteristics, including high levels of concentration, ability to detect patterns and attention to details, could be connected to the same neural plumbing that previously provided humans with an adaptive advantage. Furthermore, future treatment might be focused on pathways that would normalize, but would not eliminate the strengths of neurodiversity by finding out who the most affected cell types and genes are.
According to this 2025 Stanford study, autism does not constitute a purely pathological state but rather a shadow of adaptation the price of possessing a brain that developed to be creative, communicate, and think abstractly. As science continues to map the genetic landscape of our evolution, one thing becomes clear: the story of autism is inseparable from the story of what it means to be human.
Reference
Starr, A. L., & Fraser, H. B. (2025). A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans. Molecular Biology and Evolution, 42(9), 1–20. https://doi.org/10.1093/molbev/msaf189