Abstract Modern humans exhibit phenotypic traits that are shared across independent domestication events, suggesting the human self-domestication hypothesis. Epigenetic changes may facilitate early self-domestication in humans, since they can be the first layer of response to a novel environment. Here, we argue that fish provide model systems to study epigenetic drivers in human self-domestication. To do this, we compare genes that carry epigenetic changes in early domesticates of European sea bass with 1) anatomically modern humans and 2) neurodevelopmental cognitive disorders with abnormal self-domestication traits, i.e., schizophrenia, Williams syndrome and autism spectrum disorders. We found that genes with epigenetic changes in fish and in modern vs ancient humans were shared and were involved in processes like limb morphogenesis and phenotypes like abnormal snout morphology and hypopigmentation. Moreover, early domestication in fish and neurodevelopmental cognitive impairment in humans affected paralogue genes involved in processes such as neural crest differentiation and ectoderm differentiation. We conclude that parallel epigenetic changes may occur at the initial steps of domestication in absence of deliberate selection in phylogenetically distant vertebrates. These findings pave the way for future studies using fish as models to investigate epigenetic changes as drivers of human-self domestication and as triggers of cognitive disorders.

Fish as model systems to study epigenetic drivers in human self-domestication and neurodevelopmental cognitive disorders