Abstract
BackgroundAn essential question in evolutionary biology is whether shifts in a set of polygenic behaviors share a genetic basis across species. Such a behavioral shift is seen in the cave-dwelling Mexican tetra, Astyanax mexicanus. Relative to surface-dwelling conspecifics, cavefish do not school (asocial), are hyperactive and sleepless, adhere to a particular vibration stimulus (imbalanced attention), behave repetitively, and show elevated stress hormone levels. Interestingly, these traits largely overlap with the core symptoms of human autism spectrum disorder (ASD), raising the possibility that these behavioral traits are underpinned by a similar set of genes (i.e. a repeatedly used suite of genes).ResultHere, we explored whether modification of ASD-risk genes underlies cavefish evolution. Transcriptomic analyses revealed that > 58.5% of 3152 cavefish orthologs to ASD-risk genes are significantly up- or down-regulated in the same direction as genes in postmortem brains from ASD patients. Enrichment tests suggest that ASD-risk gene orthologs in A. mexicanus have experienced more positive selection than other genes across the genome. Notably, these positively selected cavefish ASD-risk genes are enriched for pathways involved in gut function, inflammatory diseases, and lipid/energy metabolism, similar to symptoms that frequently coexist in ASD patients. Lastly, ASD drugs mitigated cavefish’s ASD-like behaviors, implying shared aspects of neural processing.ConclusionOverall, our study indicates that ASD-risk genes and associated pathways (especially digestive, immune and metabolic pathways) may be repeatedly used for shifts in polygenic behaviors across evolutionary time.
Highlights
An essential question in evolutionary biology is whether shifts in a set of polygenic behaviors share a genetic basis across species
Overall, our study indicates that autism spectrum disorder (ASD)-risk genes and associated pathways may be repeatedly used for shifts in polygenic behaviors across evolutionary time
We found that 92.5% of 493 human ASD-risk genes
Summary
An essential question in evolutionary biology is whether shifts in a set of polygenic behaviors share a genetic basis across species. Relative to surface-dwelling conspecifics, cavefish do not school (asocial), are hyperactive and sleepless, adhere to a particular vibration stimulus (imbalanced attention), behave repetitively, and show elevated stress hormone levels. These traits largely overlap with the core symptoms of human autism spectrum disorder (ASD), raising the possibility that these behavioral traits are underpinned by a similar set of genes (i.e. a repeatedly used suite of genes). Some behavioral syndromes demonstrate that correlated behaviors can be underpinned by different genetic factors [2, 3] It is largely unknown if any particular suite of genes, or so-called ‘genetic toolkit’ [4,5,6], are modified across. Despite large differences in the complexities of their behavioral traits, vertebrates share many core characteristics of neural connectivity and molecular pathways in their innate social behaviors
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