Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

Abstract

Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism. In certain circumstances, these effects can be transmitted across several generations through epigenetic (i.e. non-DNA sequence-based rather than mutational) modifications. In this review, we summarize recent evidence on epigenetic inheritance from parental environment-induced developmental and physiological alterations in nematodes, fruit flies, zebrafish, rodents, and humans. The epigenetic modifications demonstrated to be both susceptible to modulation by environmental cues and heritable, including DNA methylation, histone modification, and small non-coding RNAs, are also summarized. We particularly focus on evidence that parental environment-induced epigenetic alterations are transmitted through both the maternal and paternal germlines and exert sex-specific effects. The thought-provoking data presented here raise fundamental questions about the mechanisms responsible for these phenomena. In particular, the means that define the specificity of the response to parental experience in the gamete epigenome and that direct the establishment of the specific epigenetic change in the developing embryos, as well as in specific tissues in the descendants, remain obscure and require elucidation. More precise epigenetic assessment at both the genome-wide level and single-cell resolution as well as strategies for breeding at relatively sensitive periods of development and manipulation aimed at specific epigenetic modification are imperative for identifying parental environment-induced epigenetic marks across generations. Considering their diverse epigenetic architectures, the conservation and prevalence of the mechanisms underlying epigenetic inheritance in non-mammals require further investigation in mammals. Interpretation of the consequences arising from epigenetic inheritance on organisms and a better understanding of the underlying mechanisms will provide insight into how gene-environment interactions shape developmental processes and physiological functions, which in turn may have wide-ranging implications for human health, and understanding biological adaptation and evolution.

Epigenetically facilitated mutational assimilation: epigenetics as a hub within the inclusive evolutionary synthesis

“…These examples show not only that the environment can affect phenotypes, but also that the resulting phenotypic change can be epigenetically transmitted through the germline for up to at least 80 generations (Vastenhouw et al ., ; review in Wang et al ., ). It should be noted that most published estimates of transgenerational persistence probably constitute minimal values because most studies stop before the disappearance of the environmental effect.…”

“…These mechanisms include epigenetics [inclusively heritable (Danchin & Wagner, ) molecular variation in gene expression without change in DNA sequence, resulting from DNA methylation or histone modifications, and often mediated by small non‐coding RNAs (sncRNAs, i.e. RNA molecules that are not translated into a protein and that are less than 200 nt in size) (Morgan et al ., ; Richards, ; Johannes, Colot & Jansen, ; Ashe et al ., ; de Vanssay et al ., ; Eichten & Borevitz, ; Cortijo et al ., ; Kronholm, ; Wang et al ., ; Nishikawa & Kinjo, )], cultural and ecological inheritance (Danchin et al ., ; Laland et al ., ; Odling‐Smee, ; Fisher & Ridley, ), as well as parental effects (Francis et al ., ; Jablonka & Raz, ; Bonduriansky et al ., ; Danchin et al ., ; Daxinger & Whitelaw, ; reviews in Mameli, ; Morgan et al ., ; Richards, ; Sharma, ; Szyf, ). In its broadest meaning, non‐genetic inheritance also includes the vertical inheritance of symbionts (Fellous et al ., ), as well as other modes of ‘inheritance’ such as prions (Manjrekar, ; Newby et al ., ) and chaperone molecules (Halfmann & Lindquist, ; Lindquist, ; Halfmann et al ., ; Saibil, ) that constitute other forms of molecular memory.…”

“…The existence of non-genetic inheritance has long been debated (among many reviews see Danchin et al, 2004Danchin et al, , 2011Mameli, 2004;Richards, 2006;Rando & Verstrepen, 2007;Franklin & Mansuy, 2010;Pigliucci & Muller, 2010;Bonduriansky, Crean & Day, 2011;Herman & Sultan, 2011;Chen, Yan & Duan, 2016b;Kronholm, 2017;Laland, 2017;Wang, Liu & Sun, 2017), but it is now widely accepted. Table 1 provides representative examples of the evidence supporting the existence and ubiquity of non-genetic inheritance in organisms ranging from unicellular, to plants, to animals including humans.…”

Daphnia magna microRNAs respond to nutritional stress and ageing but are not transgenerational

“…For example, in the rotifer Brachionus manjavac as, female offspring of older mothers show decreased life expectancy and fecundity compared to those of young mothers, and this is partially ameliorated by caloric restriction (Gribble, Jarvis, Bock, & Mark Welch, ). In rats, effects of dietary restriction have been observed up to three generations on from diet treatments (Benyshek, Johnston, & Martin, ; Wang, Liu, & Sun, ). Maternal effects on ageing have also been observed in mouse blastocysts transferred from old and young mothers into young surrogates to create a normalized in vivo maternal environment (Velazquez, Smith, Smyth, Osmond, & Fleming, ).…”

What are parental condition‐transfer effects and how can they be detected?

“…In such cases, high condition may enable parents to transfer advantageous epigenetic variants to their offspring, and the condition‐dependence of such effects may be maintained by (as yet unknown) costs of developing, maintaining, or deploying the required epigenetic machinery. For example, just as the maintenance of genome‐wide DNA methylation states is strongly age‐dependent, with deleterious changes accompanying (and perhaps causing) senescence (“epigenetic clock”: Horvath, ), stress may accelerate the clock (Horvath et al., ; Simons et al., ; Zannas et al., ), and some of these epigenetic changes may be transmissible to offspring (Skinner, ; Wang, Liu, & Sun, ). The taxonomic distribution, proximate basis, and ecological role of condition‐transfer effects in such non‐resource systems remain poorly understood.…”