Epigenetic Inheritance of Physiological Phenotypes: Occurrence, Mechanism and Inter-and Intra-individual Variation

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The exact set of traits and features possessed by an animal (phenotypes) is shaped by genetic factors provided by maternal and paternal contributions to the genome. The phenotypes are also shaped by so-called "epi-genetic" changes that impact gene expression but do not change the sequence of the DNA. This award supports a two year EAGER project that focuses on the unexplored epigenetic inheritance of modified phenotypes of a higher-order physiological process, cardiovascular performance, and how physiological variation might result from mechanistic variation. Among key novel aspects of the proposed experiments is the focus on "true" transgenerational epigenetic inheritance in non-placental animals, rather than in utero or maternal effects. This project will focus on inter- and intra-individual variation in the underlying molecular mechanisms. The significant Broader Impacts of this proposal include the cross-training of a cohort of both US students and Mexican graduate students (involving UNT's new agreement with Mexico's CONACyT funding agency). These students will receive training in the nexus of physiology and epigenetics as well as an enriched perspective on international research coordination.Three hypotheses will be tested in the course of this project: H1: The Transgenerational Epigenetic Effect. Exposure to aquatic hypoxia in mature adult zebrafish (P0) before they begin reproduction will modify cardiovascular phenotype in their offspring (F1 and possibly F2 and beyond); H2: Epigenetic Dynamics. Epigenetically-inherited cardiovascular phenotypes are highly dynamic, showing both variation between individuals and slowly disappearing (fading out) across generations; and H3: Epigenetic Mechanisms. The germ-line of the P0 generation experiences variable degrees of DNA methylation and/or histone modification that lingers through subsequent fertilization and development, which may be correlated with variably altered gene expression and hence variation in the modified physiological phenotypes in the F1 generation. Data from this study are likely to underscore an emerging yet still vaguely defined rationale for why epigenetic inheritance has been selected for as a mechanism for surviving environmental changes that span several generations. Results will be disseminated through publication in peer-reviewed journals and through presentation at scientific meetings.