How evolution explains autism rates in humans

A new paper in Molecular Biology and Evolution, published by Oxford University Press, finds that the relatively high rate of Autism-spectrum disorders in humans is likely due to how humans evolved in the past.

About one in 31 (3.2%) children in the United States has been identified with Autism Spectrum Disorder. Globally, the World Health Organization estimates that around one in 100 children have autism. From an evolutionary perspective, many scientist believe that autism and schizophrenia may be unique to humans. It is very rare to find behaviors associated with the disorders in non-human primates. In addition, behaviors associated with those disorders generally involve cognitive traits like speech production and comprehension that are either unique to or much more sophisticated in humans.

With the development of single cell RNA-sequencing, it became possible to define specific cell types across the brain. As investigators published more large-scale datasets, it became clear that the mammalian brain contains a staggering array of neuronal cell types. In addition, large-scale sequencing studies have identified extensive genetic changes in the brain unique to Homo sapiens—genomic elements that did not change much in mammalian evolution in general but evolved rapidly in humans.

While previous investigations found that some cell types have remained more consistent throughout evolution than others, the factors driving these differences in evolutionary rate remain unknown. Researchers here investigated recently published cross-species single-nucleus RNA sequencing datasets from three distinct regions of the mammalian brain. They found that the most abundant type of outer-layer brain neurons, L2/3 IT neurons, evolved exceptionally quickly in the human lineage compared to other apes. Surprisingly, this accelerated evolution was accompanied by dramatic changes in autism-associated genes, which was likely driven by natural selection specific to the human lineage. The researchers here explain that although the results strongly suggest natural selection for Autism Spectrum Disorder-associated genes, the reason why this conferred fitness benefits to human ancestors is unclear.

Answering this is difficult because we do not know what human-specific features of cognition, brain anatomy, and neuronal wiring gave human ancestors a fitness advantage, but the investigators here speculate that many of these genes are associated with developmental delay, so their evolution could have contributed to the slower postnatal brain development in humans compared to chimpanzees. Furthermore, the capacity for speech production and comprehension unique to humans is often affected by autism and schizophrenia.

It’s possible that the rapid evolution of autism-linked genes conferred a fitness advantage by slowing postnatal brain development or increasing the capacity for language; the lengthier brain development time in early childhood was beneficial to human evolution because it led to more complex thinking.

“Our results suggest that some of the same genetic changes that make the human brain unique also made humans more neurodiverse,” said the paper’s lead author, Alexander L. Starr.

The paper, “A general principle of neuronal evolution reveals a human accelerated neuron type potentially underlying the high prevalence of autism in humans,” is available (at midnight on September 9^th) at https://academic.oup.com/mbe/article-lookup/doi/10.1093/molbev/msaf189.

Direct correspondence to: 
Alexander L. Starr
Ph.D. Student in Biology
Stanford University, 
Stanford, CA 94305
astarr97@stanford.edu

To request a copy of the study, please contact:
Daniel Luzer 
daniel.luzer@oup.com