Early-life exposure to methylmercury induces reversible behavioral impairments and gene expression modifications in one isogenic lineage of mangrove rivulus fish Kryptolebias marmoratus.

Methylmercury (MeHg) is a ubiquitous bioaccumulative neurotoxicant present in aquatic ecosystems. It is known to alter behaviors, sensory functions and learning abilities in fish and other vertebrates. Developmental and early-life stages exposure to MeHg can lead to brain damage with immediate consequences on larvae behavior, but may also induce long term effects in adults after a detoxification period. However, very little is known about developmental origin of behavioral impairment in adults due to early exposure to MeHg. The aim of this study is to assess whether early-life MeHg exposure induces immediate and/or delayed effects on behaviors, related genes expression and DNA methylation (one of epigenetic mechanisms). To reach this goal, newly hatched larvae of mangrove rivulus fish, Kryptolebias marmoratus, were exposed to two sub-lethal concentrations of MeHg (90 µg/L and 135 µg/L) for 7 days, and immediate and delayed effects were assessed respectively in 7 dph (days post-hatching) and 90 dph fish. This species naturally produces isogenic lineages due to its self-fertilizing reproduction system, which is unique among vertebrates. It allows to study how environment stressors can influence organism's phenotype while minimizing genetic variability. As results, both MeHg exposures are associated with a decreased foraging efficiency and thigmotaxis, and a dose-dependent reduction in larvae locomotor activity. Regarding molecular analysis in larvae whole bodies, both MeHg exposures induced significant decreased expression of DNMT3a, MAOA, MeCP2 and NIPBL, and significant increase of GSS, but none of those genes underwent methylation changes in targeted CpGs. None of significant behavioral and molecular impairments observed in 7-dph larvae were found in 90-dph adults, which highlight a distinction between immediate and delayed effects of developmental MeHg exposure. Our results suggest implications of aminergic system and its neurotransmitters, redox/methylation trade-off and possibly other epigenetic mechanisms in MeHg neurotoxicity underlying behavioral alterations in rivulus.

The Role of Stochasticity in the Origin of Epigenetic Variation in Animal Populations.

Epigenetic mechanisms such as DNA methylation modulate gene expression in a complex fashion are consequently recognized as among the most important contributors to phenotypic variation in natural populations of plants, animals, and microorganisms. Interactions between genetics and epigenetics are multifaceted and epigenetic variation stands at the crossroad between genetic and environmental variance, which make these mechanisms prominent in the processes of adaptive evolution. DNA methylation patterns depend on the genotype and can be reshaped by environmental conditions, while transgenerational epigenetic inheritance has been reported in various species. On the other hand, DNA methylation can influence the genetic mutation rate and directly affect the evolutionary potential of a population. The origin of epigenetic variance can be attributed to genetic, environmental, or stochastic factors. Generally less investigated than the first two components, variation lacking any predictable order is nevertheless present in natural populations and stochastic epigenetic variation, also referred to spontaneous epimutations, can sustain phenotypic diversity. Here, potential sources of such stochastic epigenetic variability in animals are explored, with a focus on DNA methylation. To this day, quantifying the importance of stochasticity in epigenetic variability remains a challenge. However, comparisons between the mutation and the epimutation rates showed a high level of the latter, suggesting a significant role of spontaneous epimutations in adaptation. The implications of stochastic epigenetic variability are multifold: by affecting development and subsequently phenotype, random changes in epigenetic marks may provide additional phenotypic diversity, which can help natural populations when facing fluctuating environments. In isogenic lineages and asexually reproducing organisms, poor or absent genetic diversity can hence be tolerated. Further implication of stochastic epigenetic variability in adaptation is found in bottlenecked invasive species populations and populations using a bet-hedging strategy.