A Unified Approach to the Evolutionary Consequences of Genetic and Nongenetic Inheritance

Day, Troy; Bonduriansky, Russell

doi:10.1086/660911

Cited by 268 publications

(295 citation statements)

References 59 publications

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“…Several molecular mechanisms have been implicated, ranging from inherited RNAs to chemically modified DNA and proteins (51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61). These transgenerational effects have important implications for our understanding of adaptation and evolution, the origins of phenotypic variation and disease risk, and the molecules in addition to DNA that can be the basis for inheritance (18,62,63).…”

Section: Discussionmentioning

confidence: 99%

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Environmental agents and genetic variants can induce heritable epigenetic changes that affect phenotypic variation and disease risk in many species. These transgenerational effects challenge conventional understanding about the modes and mechanisms of inheritance, but their molecular basis is poorly understood. The Deadend1 (Dnd1) gene enhances susceptibility to testicular germ cell tumors (TGCTs) in mice, in part by interacting epigenetically with other TGCT modifier genes in previous generations. Sequence homology to A1cf, the RNA-binding subunit of the ApoB editing complex, raises the possibility that the function of Dnd1 is related to Apobec1 activity as a cytidine deaminase. We conducted a series of experiments with a genetically engineered deficiency of Apobec1 on the TGCT-susceptible 129/Sv inbred background to determine whether dosage of Apobec1 modifies susceptibility, either alone or in combination with Dnd1, and either in a conventional or a transgenerational manner. In the paternal germ-lineage, Apobec1 deficiency significantly increased susceptibility among heterozygous but not wild-type male offspring, without subsequent transgenerational effects, showing that increased TGCT risk resulting from partial loss of Apobec1 function is inherited in a conventional manner. By contrast, partial deficiency in the maternal germ-lineage led to suppression of TGCTs in both partially and fully deficient males and significantly reduced TGCT risk in a transgenerational manner among wild-type offspring. These heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage. These results suggest that Apobec1 plays a central role in controlling TGCT susceptibility in both a conventional and a transgenerational manner.epigenetics | testicular cancer | gametogenesis | epistasis E stablishing the genetic basis and mode of inheritance for most traits and diseases has proven to be remarkably elusive (1). Susceptibility to testicular germ cell tumors (TGCTs) is illustrative (2). Testicular cancer is the most common malignancy affecting young men (3), more than 90% of testicular cancers result from TGCTs (4), TGCTs rank third in heritability among all cancers (5), and family history is the strongest known risk factor with a two-to sixfold increase among sons and a 5-to 19-fold increase among brothers of affected individuals (6-9). Despite the strong evidence for heritability, the only TGCT susceptibility factors identified in genome-wide association studies are the gr/gr deletion on the Y chromosome and autosomal variants in KITLG, SPRY4, BAK1, and DMRT1, which together account for less than 10% of risk (10-14). The substantial difference in prevalence between sons and brothers of cases and the epidemiological evidence for maternal estrogens, birth order, birth weight, and other factors (15-17) together raise the possibility that maternal conditions, epigenetic effects, and perhaps unconventional modes of inheritance also contribute to TG...

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Section: Discussionmentioning

confidence: 99%

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Nelson

Heaney

Tesar

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Such 'transgenerational plasticity' occurs when the environment experienced by parents alters the phenotypes of subsequent generations [4,5]. Transgenerational responses have been documented in many organisms [6] for a variety of environmental perturbations [3] and are postulated to have far-reaching consequences for population dynamics [7], community interactions [8] and the rate and direction of evolutionary change [9][10][11]. Yet, despite widespread appreciation for the existence of transgenerational plasticity ( [11,12], but see [13,14]), our understanding of the evolution of transgenerational responses is limited.…”

Section: Introductionmentioning

confidence: 99%

Predator-induced phenotypic plasticity within- and across-generations: a challenge for theory?

et al. 2015

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Much work has shown that the environment can induce non-genetic changes in phenotype that span multiple generations. Theory predicts that predictable environmental variation selects for both increased within-and acrossgeneration responses. Yet, to the best of our knowledge, there are no empirical tests of this prediction. We explored the relationship between within-versus across-generation plasticity by evaluating the influence of predator cues on the life-history traits of Daphnia ambigua. We measured the duration of predator-induced transgenerational effects, determined when transgenerational responses are induced, and quantified the cues that activate transgenerational plasticity. We show that predator exposure during embryonic development causes earlier maturation and increased reproductive output. Such effects are detectable two generations removed from predator exposure and are similar in magnitude in response to exposure to cues emitted by injured conspecifics. Moreover, all experimental contexts and traits yielded a negative correlation between within-versus across-generation responses. That is, responses to predator cues within-and across-generations were opposite in sign and magnitude. Although many models address transgenerational plasticity, none of them explain this apparent negative relationship between within-and across-generation plasticities. Our results highlight the need to refine the theory of transgenerational plasticity.

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“…[34][35][36], reviewed in [26]). Most models study how the extent of incomplete epigenetic resetting influences the spread and maintenance of genetic or epigenetic variation.…”

Section: Introductionmentioning

confidence: 99%

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

2015

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Resetting of epigenetic marks, such as DNA methylation, in germ cells or early embryos is not always complete. Epigenetic states may therefore persist, decay or accumulate across generations. In spite of mounting empirical evidence for incomplete resetting, it is currently poorly understood whether it simply reflects stochastic noise or plays an adaptive role in phenotype determination. Here, we use a simple model to show that incomplete resetting can be adaptive in heterogeneous environments. Transmission of acquired epigenetic states prevents mismatched phenotypes when the environment changes infrequently relative to generation time and when maternal and environmental cues are unreliable. We discuss how these results may help to interpret the emerging data on transgenerational epigenetic inheritance in plants and animals.

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A Unified Approach to the Evolutionary Consequences of Genetic and Nongenetic Inheritance

Cited by 268 publications

References 59 publications

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability

Predator-induced phenotypic plasticity within- and across-generations: a challenge for theory?

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

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