Multi-omics data analysis supporting inheritance of acquired traits in humans

Abstract Experimental evidence exists to support germline mediated non-DNA sequence-based inheritance of environmentally induced traits in animals including mammalian models. Epidemiological studies also suggest possible presence of epigenetic inheritance in humans. Here, an unbiased analysis of available human and animal model multi-omics data is presented that supports inheritance of induced traits in humans. First, in an analysis feasibility survey, physical exercise was identified as the lone environmental factor that affects conserved physiological pathways and induces inheritance in animal models, and at the same time, the effects of which on human cohort sperm DNA methylome, and human cohort, rat, mouse and Drosophila coding and/or non-coding somatic transcriptome have been multiply described. The hypothesis was thus tested that exercise associated differentially methylated genes (DMGs) in human sperm are specifically enriched for exercise associated differentially expressed mRNAs (DEmRNAs) in human and animal model somatic tissues, the sperm DMGs and somatic DEmRNAs overrepresent common gene ontology terms, the sperm promoter DMGs and the somatic DEmRNAs in humans are inversely regulated, and the sperm DMGs overrepresent targets of exercise associated differentially expressed miRNAs (DEmiRNAs) in human somatic tissues. For controlling the analysis, bariatric surgery, identified as an exercise matching factor for which human cohort sperm DNA methylome and somatic transcriptome datasets are multiply available, was used. Remarkably, the hypothesis was supported in all the above pre-specified tests. This suggests that acquired somatic gene expression changes are encoded as DNA methylation alterations in human germline, supporting existence of epigenetic inheritance in our species.