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 at Stanford University have 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.

More common neuronal cell types evolve more slowly than rare types

a) Rationale for the hypothesis that more common neuronal types might evolve more slowly than rarer types. A gene expression change in a common cell type has a large negative effect on fitness, whereas the same change in a rarer cell type has a smaller effect. Made with BioRender. b) Left: outline of our data analysis strategy. SnRNA-seq from the MTG of five species (14 subclasses of neurons) was used to estimate each cell type’s proportion and pairwise divergence between species. Right: plot showing the correlation between the neuronal subclass proportion (log10 scale on the x-axis) and the subclass-specific divergence between the human and the marmoset in the MTG. A representative iteration from 100 independent down-samplings is shown. Spearman’s ρ and P-value shown are the median across 100 independent down-samplings (see Materials and Methods for details). The line and shaded region are the line of best fit from a linear regression and 95% confidence interval, respectively. c) Same as b), but snRNA-seq from the DLPFC (17 subclasses of neurons) of four species was analyzed. d) Same as b), but snRNA-seq from M1 (12 subclasses of neurons) of three species was analyzed.

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.

Source – Oxford University Press USA