Human brain evolution may explain the rapid increase in autism rates

Autism has many causes, but one question keeps coming up: why are autism rates higher in humans than in other animals? A new line of evidence points to how certain brain cell types changed during human evolution.

A new study maps a principle of brain cell evolution and ties it to genes linked with autism. The work leans on large data sets to compare humans with other primates.

Evolution and autism

Lead author Alexander L. Starr of Stanford University’s Department of Biology, led the work. His team examined how brain cell types vary across species and how fast their gene activity shifted over time.

“The overall observed autism spectrum disorder (ASD) prevalence was 32.2 per 1,000 (one in 31) children aged 8 years,” wrote K. A. Shaw and colleagues in a CDC surveillance report regarding the prevalence in the United States.

ADS is a neurodevelopmental condition that affects social interaction, communication, and behavior. 

Global autism context

Worldwide, the WHO estimates that about one in 100 children has autism, with wide uncertainty in many countries. Reporting varies, but the gap between global and U.S. estimates frames a real public health concern.

These numbers set the stage for asking whether uniquely human brain features helped raise the likelihood of autism. The new work explores that possibility without claiming a single cause.

Neurons in autism

The study highlights the most common outer layer excitatory neurons in the neocortex, called L2/3 IT neurons.

These cells connect areas of the cortex and support higher cognition in humans. The authors find that this neuron class evolved unusually fast along the human lineage.

Independent single cell studies show that layers 2 and 3 excitatory neurons carry strong autism-related changes in human brain tissue.

That pattern emerged clearly in recent Science work using single cell genomics.

Testing autism and evolution

They used single cell RNA sequencing to define cell types and compare gene expression across species.

That approach reveals how active each gene is in each cell type, which is a direct window into cell identity and function.

The researchers then looked for shifts in the expression of genes linked to autism in L2/3 IT neurons. They found a marked tilt toward lower expression in humans compared to chimpanzees.

Evolution favored genes

To ask whether evolution favored those shifts, the team turned to allele-specific expression (ASE) analyses in human-chimp hybrid cortical cells.

This method holds the cellular environment constant and tests whether one species’ version of a gene is systematically higher or lower, a signal of changes in local gene regulation. 

The hybrid cell approach documents robust ASE signals that reject a neutral model and support lineage-specific selection on autism-linked genes.

The pattern points to polygenic positive selection acting on many genes at once. In other words, small regulatory changes stacked up across numerous genes in a way that natural selection likely favored in human ancestors.

Evolution in brain cells

The study also proposes a general rule. More abundant neuron types tend to change more slowly across species. The surprise here is that L2/3 IT neurons, despite being abundant, show unusually fast evolution in humans.

That outlier status is part of the story linking these neurons to autism. It suggests that human-specific pressures rewired gene expression in a cell class that is central to cortical communication.

Autism and human evolution

What advantage could lower expression of autism-linked genes provide. One idea is a longer window of postnatal brain development in humans, which supports learning and complex cognition.

Another idea centers on language. Traits tied to speech production and comprehension are uniquely rich in humans and often affected in autism, so gene shifts that boosted language capacity could have been favored historically.

DNA in autism evolution

The findings align with prior work on human accelerated regions. These are stretches of DNA that changed rapidly in our lineage and have been implicated in social and cognitive traits, including autism susceptibility.

Together, the neuron-specific results and the genomic context point in the same direction.

Human evolution likely nudged regulatory programs in neurons that matter for higher cognition, with a side effect of increasing autism risk.

Significance of the study

The authors do not say that autism has a single evolutionary cause. They also do not claim that every gene linked to autism followed the same path.

The message is more careful. A coordinated shift in gene expression in a key neuron type likely raised sensitivity to additional genetic or environmental factors in humans.

Better mechanistic maps can sharpen targets for research and, over time, for therapies. They can also inform realistic expectations about what biology can and cannot explain.

Public health planners can hold two truths at once. Diagnostic practices shape measured prevalence, and biology still matters deeply in who needs support and when.

The study is published in Molecular Biology and Evolution.

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