Image: Gerd Altmann/Pixabay
Accelerated evolution of interneurons may underlie the prevalence of autism in humans.
Autism may have arisen through evolutionary adaptations of the human brain. Downregulation of certain genes associated with autism conferred fitness advantages on our ancestors, two neurobiologists from Stanford University in the United States suspect (Molecular Biology and Evolution, 9 September). The researchers find the altered gene expression in humans in neurons of layers 2 and 3 of the cerebral cortex.
Gene expression patterns
The American researchers were not initially looking for an explanation for the prevalence of autism in humans. They were primarily interested in whether gene expression patterns in abundant cell types are more conserved than in less abundant ones. The reasoning: a change in a highly abundant cell type has greater consequences and will therefore occur less frequently. This turns out to be broadly true, as the two neurobiologists demonstrate in a meta-analysis. They compare gene expression patterns of various brain cell types across different species, using three existing datasets. In general, the gene expression patterns of cell types that are well represented in the brain do indeed show greater similarity across species than is the case for rare cell types.
Accelerated evolution
So-called interneurons – also known as relay cells – are an exception to this rule. Interneurons on the outer surface of the brain, in layers 2 and 3, are extremely abundant. Yet in humans they show markedly divergent expression compared with other species. This points to accelerated evolution of this cell type in humans, the researchers claim. Among humans themselves, variability in gene expression in these neurons was relatively low.
The American researchers then examined various datasets of genes that humans express at higher or lower levels than chimpanzees, and that are linked to particular traits. For the rapidly evolved interneurons, what stood out most was the low expression of autism-related genes in humans. Gorillas showed expression levels for these genes comparable to those of chimpanzees; humans are the outlier.
Gorillas showed expression levels for these genes comparable to those of chimpanzees; humans are the outlier
Data from organoid experiments confirm the reduced expression of autism genes in humans relative to chimpanzees, and point to selection acting on these genes in humans. Notably, all autism-related genes show reduced expression. These genes may be part of a broader group that was subject to selection, with autism-related genes falling within it by chance. The reduced expression likely means that the ‘threshold’ for autism is reached more readily in humans than in chimpanzees.
As to why divergent expression of autism-related genes once conferred an evolutionary advantage in humans, the neurobiologists remain in the dark for now. The reduced expression may have slowed brain development, they speculate, allowing the human brain to continue developing for longer after birth. Another possibility is that the reduced expression represents a compensatory mechanism – for instance, to maintain the balance between inhibitory and excitatory neurons in the brain. That balance was subject to change as the human brain grew larger over the course of evolution.