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'Non-Genetic' Inheritance: Insights from Molecular-Evolutionary Crosstalk

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'Non-Genetic' Inheritance: Insights from Molecular-Evolutionary Crosstalk Adrian-Kalchhauser et al / Understanding NGI: Insights from Molecular-Evolutionary Crosstalk / EcoEvoRxiv 20200501 Understanding 'Non-genetic' Inheritance: Insights from Molecular-Evolutionary Crosstalk Irene Adrian-Kalchhauser1, Sonia E. Sultan2, Lisa Shama3, Helen Spence-Jones4, Stefano Tiso5, Claudia Isabelle Keller Valsecchi6, Franz J. Weissing5 Addresses 1Centre for Fish and Wildlife Health, Department for Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland 2Biology Department, Wesleyan University, Middletown CT 06459 USA 3Coastal Ecology Section, Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, Wadden Sea Station Sylt, Hafenstrasse 43, 25992 List, Germany 4Centre for Biological Diversity, School of Biology, University of St Andrews, UK 5Groningen Institute for Evolutionary Life Sciences, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands 6Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany Corresponding author: Adrian-Kalchhauser, I. ([email protected]) Keywords epigenetics, epiallelic variation, methylation, transgenerational effects, inherited gene regulation, gene regulatory network model Abstract Understanding the evolutionary and ecological roles of 'non-genetic' inheritance is daunting due to the complexity and diversity of epigenetic mechanisms. We draw on precise insights from molecular structures and events to identify three general features of 'non-genetic' inheritance systems that are central to broader investigations: (i) they are functionally interdependent with, rather than separate from, DNA sequence; (ii) each of these mechanisms is not uniform but instead varies phylogenetically and operationally; and (iii) epigenetic elements are probabilistic, interactive regulatory factors and not deterministic 'epi-alleles' with defined genomic locations and effects. We explain each feature and offer research recommendations. Finally, we consider existing evolutionary models for 'non-genetic' inheritance and present a new model that implements a unifying inherited gene regulation approach. Page 1 of 22 Adrian-Kalchhauser et al / Understanding NGI: Insights from Molecular-Evolutionary Crosstalk / EcoEvoRxiv 20200501 Inheritance beyond DNA poses key questions for evolution and ecology Biologists are currently engaged in a lively fear response to the threat stimulus [25]. Targeted conversation about whether it is necessary to expand defensive responses are also initiated by juvenile our view of biological inheritance to include 'non- plants in many taxa, as a result of inherited genetic' factors [1–3]. In particular, mechanisms such modifications induced in parents attacked by as DNA methylation, histone modifications, and small herbivores or pathogens [26]. In Mimulus, for instance, non-coding RNAs have been interpreted as additional simulated insect damage to the leaves of parent 'streams' of phenotypic information distinct from DNA plants resulted in substantial down-regulation of a sequence transmission [4–8]. In comparison with DNA transcription factor in their progeny, leading to altered sequence variation, which is transmitted with great expression of over 900 genes [27] and increased fidelity across numerous generations, these factors production of defensive leaf trichomes [28]. Although have complex and potentially unpredictable dynamics: the paternal transmission mechanism of this inherited they may arise stochastically or be induced by specific effect is yet undetermined, the maternal component is environmental conditions, and they may persist from transmitted by changes in DNA methylation [29]. one to several (or possibly many) generations Environmentally-induced methylation changes are (reviewed by [9–11] in plants and by [12,13] in also implicated in the production of drought-tolerant animals; further references in [14,15]). Biologists in and shade-adaptive phenotypes by offspring of many fields are now confronting an unexpected correspondingly stressed parental Polygonum plants question: Must we fundamentally revise our [30,31]; such induced methylation changes appear to understanding of inheritance to incorporate these new be widespread in plants [3,11]. insights? Here, a group of molecular and evolutionary biologists join forces to collectively clarify the empirical Because parentally-induced effects could cause foundation for bringing these findings into evolutionary specific adaptive adjustments in many individuals (and and ecological research. their descendants) in a population after only one generation, they are of particular interest to ecologists For evolutionary biologists, the phenotypic impact of and evolutionary biologists as a potential source of inherited 'non-genetic' factors and their potential tolerance to climate change and other novel, rapidly contribution to evolutionary adaptation and unfolding challenges [32,33]. A common reef fish diversification are pressing issues (note that below the provides an intriguing recent example: Ryu and term non-genetic is subjected to critique, hence the colleagues [34] showed that juvenile Acanthochromis quotes). Although many empirical questions remain were able to acclimate successfully to elevated water [16,17], mounting evidence indicates that temperatures simulating future marine conditions transgenerational mechanisms may indeed (+3°C), as a result of inherited methylation changes to substantially influence phenotypic outcomes in a wide numerous genes involved in oxygen consumption and range of organisms. In some cases, the inherited metabolism that were induced in parents exposed to effects are negative. For instance, mammalian or elevated temperatures. A similar transgenerational insect parents with a nutrient-poor, high-fat, or high- effect was found in Acanthochromis in response to a sugar diet may transmit to offspring altered DNA second dimension of global change – ocean methylation states or tRNA fragments that result in acidification. Expression of numerous genes was metabolic or developmental disorders [18–20]. altered in individual offspring exposed to elevated Alternatively, stressful maternal or paternal conditions CO2, but only if parent fish had not previously been may induce specific, gametically transmitted changes exposed to high CO2, and some epigenetic regulator that promote adaptive phenotypes in offspring genes exhibited divergence due to parental phenotype encountering similar stresses. Such inherited but non- [35]. sequence based adaptations have been documented in a vast array of taxa (reviewed by [21–24]), although In addition to phenotypic effects on individual precise molecular mechanisms for these organisms, 'non-genetic' factors may play important transgenerational effects have been ascertained in roles in adaptive evolution. Either induced or relatively few cases. In one study of mammalian spontaneous epigenetic variants may contribute to behavior, male mice that were experimentally heritable variation in natural populations [36–38], conditioned to have a fear response to a specific odor potentially providing additional evolutionary potential produced sperm in which the relevant odor receptor [6]. If sufficiently plentiful and stable, such was hypomethylated, such that their progeny showed heterogeneous epigenetic states could provide an altered neuroanatomy and expressed the appropriate alternative substrate of standing variation to fuel Page 2 of 22 Adrian-Kalchhauser et al / Understanding NGI: Insights from Molecular-Evolutionary Crosstalk / EcoEvoRxiv 20200501 natural selection for local population divergence [39– ancestor (transgenerational epigenetic inheritance), or 41]. Although previously rare, studies of epigenetic derived from locally selected and stable epigenetic variation in wild populations have recently become variants (often termed 'epialleles' or 'epimutations') more common (e.g. [42]; further examples listed in (e.g. [39]). [43–47]). Such variation has been shown to play a role in several aspects of population dynamics relevant to Importantly, even if epigenetic factors are transient local differentiation (e.g., invasion potential [48,49], relative to DNA sequence variants (i.e. inherited for migration propensity [50], developmental morph only one to several generations), they may determination [51,52], and host-parasite interactions substantially change selection gradients and hence [53]). In some cases, population comparisons across have far-reaching evolutionary impact [5,56,57]. environmental or climatic gradients have Theoretical models show that the inheritance of ‘non- demonstrated a role for epigenetic modifications in genetic’ factors affects the speed of evolution and the local adaptation [38,54,55]. However, it is challenging precision of adaptation as well as the genetic for field population surveys to determine whether parameters (such as heritability) which are used for epigenetic variation has been directly induced by making evolutionary inferences (discussion and environmental conditions, inherited from an induced further references in [15,58]). Toward a more precise view of 'non-genetic' inheritance Although much progress has been made in summarising existing terms and their implications; a understanding the ecological and evolutionary role of theory box briefly examines existing evolutionary 'non-genetic' inheritance, a sound understanding is models for 'non-genetic' inheritance and presents a hampered by three
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