Anastasiadi, D. | Search bioRxiv

bioRxiv2025

DNA Methylation in Sex Chromosomes and Genes under Selection Underpins the Emergence of Sexual Size Dimorphism

Sexual size dimorphism (SSD) refers to the differences in body size between males and females. Epigenetics such as methylation contribute to shaping phenotypes, nevertheless, their role in SSD is still unclear. Here, we used Cynoglossus semilaevis, a species with larger females known as female-biased SSD, as a model to investigate the role of methylation in the emergence and regulation of SSD. Methylomes and transcriptomes were constructed in four tissues (brain, liver, muscle, and gonad) from three key life stages: juveniles (3-months post fertilization), male mature stage (1-year post fertilization; ypf), and female mature stage (3 ypf). In 1 ypf and 3 ypf females showed lower methylation, while the number of differentially methylated regions between sexes increased during the lifetime. Genes at the top of the growth hormone/insulin-like growth factor (GH/IGF) axis and hypothalamus-pituitary-gonadal axis (gh1, igf1, gnrhr2r-like, err{gamma}, etc.) showed differential methylation between sexes, consistent with sex-related differences in growth. The female-specific W chromosome showed higher methylation than the autosomes or the Z chromosome. Genes of the IGF signaling network that negatively regulate growth and located on W chromosome were hyper-methylated than their Z homologs. Furthermore, genes with a faster evolutionary rate in C. semilaevis exhibited lower methylation levels than the background genes, suggesting an important evolutionary role for DNA methylation in shaping SSD. Our results provide a comprehensive depiction of methylation regulation of SSD in vertebrates, and improve our understanding of how methylation regulation can help organisms to respond to natural selection, and allocate resources between the sexes.

developmental biology↗

bioRxiv2022

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

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.

evolutionary biology↗