Non-conflict theories for the evolution of genomic imprinting

Theories focused on kinship and the genetic conflict it induces are widely considered to be the primary explanations for the evolution of genomic imprinting. However, there have appeared many competing ideas that do not involve kinship/conflict. These ideas are often overlooked because kinship/conflict is entrenched in the literature, especially outside evolutionary biology. Here we provide a critical overview of these non-conflict theories, providing an accessible perspective into this literature. We suggest that some of these alternative hypotheses may, in fact, provide tenable explanations of the evolution of imprinting for at least some loci.     

The evolution of X-linked genomic imprinting

We develop a quantitative genetic model to investigate the evolution of X-imprinting. The model compares two forces that select for X-imprinting: genomic conflict caused by polygamy and sex-specific selection. Genomic conflict can only explain small reductions in maternal X gene expression and cannot explain silencing of the maternal X. In contrast, sex-specific selection can cause extreme differences in gene expression, in either direction (lowered maternal or paternal gene expression), even to the point of gene silencing of either the maternal or paternal copy. These conclusions assume that the Y chromosome lacks genetic activity. The presence of an active Y homologue makes imprinting resemble the autosomal pattern, with active paternal alleles (X- and Y-linked) and silenced maternal alleles. This outcome is likely to be restricted as Y-linked alleles are subject to the accumulation of deleterious mutations. Experimental evidence concerning X-imprinting in mouse and human is interpreted in the light of these predictions and is shown to be far more easily explained by sex-specific selection.     

Selective abortion and the evolution of genomic imprinting

Mothers can determine which genotypes of offspring they will produce through selective abortion or selective implantation. This process can, at some loci, favour matching between maternal and offspring genotype whereas at other loci mismatching may be favoured (e.g. MHC, HLA). Genomic imprinting generally renders gene expression monoallelic and could thus be adaptive at loci where matching or mismatching is beneficial. This hypothesis, however, remains unexplored despite evidence that loci known to play a role in genetic compatibility may be imprinted. We develop a simple model demonstrating that, when matching is beneficial, imprinting with maternal expression is adaptive because the incompatible paternal allele is not detected, protecting offspring from selective abortion. Conversely, when mismatching is beneficial, imprinting with paternal expression is adaptive because the maternal genotype is more able to identify the presence of a foreign allele in offspring. Thus, imprinting may act as a genomic ‘cloaking device’ during critical periods in development when selective abortion is possible.     

Convergent evolution of genomic imprinting in plants and mammals

Parental genomic imprinting is characterized by the expression of a selected panel of genes from one of the two parental alleles. Recent evidence shows that DNA methylation and histone modifications are responsible for this parent-of-origin-dependent expression of imprinted genes. Because similar epigenetic marks have been recruited independently in plants and mammals, the only organisms in which imprinted gene loci have been identified so far, this phenomenon represents a case for convergent evolution. Here we discuss the emerging parallels in imprinting in both taxa. We also describe the significance of imprinting for reproduction and discuss potential models for its evolution.     

Gene interactions in the evolution of genomic imprinting

Numerous evolutionary theories have been developed to explain the epigenetic phenomenon of genomic imprinting. Here, we explore a subset of theories wherein non-additive genetic interactions can favour imprinting. In the simplest genic interaction—the case of underdominance—imprinting can be favoured to hide effectively low-fitness heterozygous genotypes; however, as there is no asymmetry between maternally and paternally inherited alleles in this model, other means of enforcing monoallelic expression may be more plausible evolutionary outcomes than genomic imprinting. By contrast, more successful interaction models of imprinting rely on an asymmetry between the maternally and paternally inherited alleles at a locus that favours the silencing of one allele as a means of coordinating the expression of high-fitness allelic combinations. For example, with interactions between autosomal loci, imprinting functionally preserves high-fitness genotypes that were favoured by selection in the previous generation. In this scenario, once a focal locus becomes imprinted, selection at interacting loci favours a matching imprint. Uniparental transmission generates similar asymmetries for sex chromosomes and cytoplasmic factors interacting with autosomal loci, with selection favouring the expression of either maternal or paternally derived autosomal alleles depending on the pattern of transmission of the uniparentally inherited factor. In a final class of models, asymmetries arise when genes expressed in offspring interact with genes expressed in one of its parents. Under such a scenario, a locus evolves to have imprinted expression in offspring to coordinate the interaction with its parent''s genome. We illustrate these models and explore key links and differences using a unified framework.     

The evolution of genomic imprinting via variance minimization: an evolutionary genetic model

A small number of mammalian loci exhibit genomic imprinting, in which only one copy of a gene is expressed while the other is silenced. At some such loci, the maternally inherited allele is inactivated; others show paternal inactivation. Several hypotheses have been put forward to explain how this genetic system could have evolved in the face of the selective advantages of diploidy. In this study, we examine the variance-minimization hypothesis, which proposes that imprinting arose through selection for reduced variation in levels of gene expression. We present an evolutionary genetic model incorporating both this selection pressure and deleterious mutations to elucidate the conditions under which imprinting could evolve. Our analysis implies that additional mechanisms such as genetic drift are required for imprinting to evolve from an initial nonimprinting state. Other predictions of this hypothesis do not appear to fit the available data as well as predictions for two alternative hypotheses, genetic conflict and the ovarian time bomb. On the basis of this evidence, we conclude that the variance-minimization hypothesis appears less adequate to explain the evolution of genomic imprinting.     

Genetic conflicts,multiple paternity and the evolution of genomic imprinting.

We present nine diallelic models of genetic conflict in which one allele is imprintable and the other is not to examine how genomic imprinting may have evolved. Imprinting is presumed to be either maternal (i.e., the maternally derived gene is inactivated) or paternal. Females are assumed to be either completely monogamous or always bigamous, so that we may see any effect of multiple paternity. In contrast to previous verbal and quantitative genetic models, we find that genetic conflicts need not lead to paternal imprinting of growth inhibitors and maternal imprinting of growth enhancers. Indeed, in some of our models--those with strict monogamy--the dynamics of maternal and paternal imprinting are identical. Multiple paternity is not necessary for the evolution of imprinting, and in our models of maternal imprinting, multiple paternity has no effect at all. Nevertheless, multiple paternity favors the evolution of paternal imprinting of growth inhibitors and hinders that of growth enhancers. Hence, any degree of multiple paternity means that growth inhibitors are more likely to be paternally imprinted, and growth enhancers maternally so. In all of our models, stable polymorphism of imprinting status is possible and mean fitness can decrease over time. Neither of these behaviors have been predicted by previous models.     

Coadaptation and conflict,misconception and muddle,in the evolution of genomic imprinting

Common misconceptions of the ‘parental conflict'' theory of genomic imprinting are addressed. Contrary to widespread belief, the theory defines conditions for cooperation as well as conflict in mother–offspring relations. Moreover, conflict between genes of maternal and paternal origin is not the same as conflict between mothers and fathers. In theory, imprinting can evolve either because genes of maternal and paternal origin have divergent interests or because offspring benefit from a phenotypic match, or mismatch, to one or other parent. The latter class of models usually require maintenance of polymorphism at imprinted loci for the maintenance of imprinted expression. The conflict hypothesis does not require maintenance of polymorphism and is therefore a more plausible explanation of evolutionarily conserved imprinting.     

C-S-R triangle theory: community-level predictions, tests, evaluation of criticisms, and relation to other theories

Grime's C - S - R triangle theory has been discussed in plant ecology for two decades, but it has rarely been tested, and not often dispassionately evaluated. We consider the theory from a community viewpoint, and attempt to develop and test predictions for plant communities. C - S - R assumes that in high-disturbance (ruderal, R ) patches or habitats, competition will be absent, or low in intensity. Testing this is problematic because of the difficulty of defining the intensity of competition, and we could find no rigorous evidence to support or refute the prediction. The theory also implies that in high-disturbance habitats there will be no difference in species composition between 'competition' and 'stress' sites, but from available evidence this does not seem to be true. C - S - R assumes that in stressful ( S ) habitats, competition will be low. This assumption is difficult to define or test, because of the overall difference in plant growth rate between habitats. A prediction from the theory is that in stressful habitats autosuccession should occur, i.e. that the climax species should regenerate directly, with no specialist secondary pioneer ( R ) species. There is some evidence that autosuccession occurs under the most extreme stresses of various types. Previous criticisms of C - S - R are evaluated. Only a few are considered valid, mainly those that emphasise that C - S - R theory is a considerable simplification of reality. Previous tests of C - S - R theory appear to be inconclusive. C - S - R theory is basically a combination of r / K theory and Leaf Amortisation theory. We conclude that there is limited support for the C - S - R theory. Whether the gain in generality that the theory offers justifies the loss via simplification that it involves is still an open question. As formulated, it has limited utility as a predictive model in community ecology. Yet, it is currently the most comprehensive and coherent theory for community ecology.     

Mammalian viviparity: a complex niche in the evolution of genomic imprinting

Evolution of mammalian reproductive success has witnessed a strong dependence on maternal resources through placental in utero development. Genomic imprinting, which has an active role in mammalian viviparity, also reveals a biased role for matrilineal DNA in its regulation. The co-existence of three matrilineal generations as one (mother, foetus and post-meiotic oocytes) has provided a maternal niche for transgenerational co-adaptive selection pressures to operate. In utero foetal growth has required increased maternal feeding in advance of foetal energetic demands; the mammary glands are primed for milk production in advance of birth, while the maternal hypothalamus is hormonally primed by the foetal placenta for nest building and post-natal care. Such biological forward planning resulted from maternal–foetal co-adaptation facilitated by co-expression of the same imprinted allele in the developing hypothalamus and placenta. This co-expression is concurrent with the placenta interacting with the adult maternal hypothalamus thereby providing a transgenerational template on which selection pressures may operate ensuring optimal maternalism in this and the next generation. Invasive placentation has further required the maternal immune system to adapt and positively respond to the foetal allotype. Pivotal to these mammalian evolutionary developments, genomic imprinting emerged as a monoallelic gene dosage regulatory mechanism of tightly interconnected gene networks providing developmental genetic stability for in utero development.     

Host defenses to transposable elements and the evolution of genomic imprinting

Genomic imprinting is the differential expression of maternally and paternally inherited alleles of specific genes. Several organismic level hypotheses have been offered to explain the evolution of genomic imprinting. We argue that evolutionary explanations of the origin of imprinting that focus exclusively on the organismic level are incomplete. We propose that the complex molecular mechanisms that underlie genomic imprinting originally evolved as an adaptive response to the mutagenic potential of transposable elements (TEs). We also present a model of how these mechanisms may have been co-opted by natural selection to evolve molecular features characteristic of genomic imprinting.     

Intralocus sexual conflict can drive the evolution of genomic imprinting

Genomic imprinting is a phenomenon whereby the expression of an allele differs depending upon its parent of origin. There is an increasing number of examples of this form of epigenetic inheritance across a wide range of taxa, and imprinting errors have also been implicated in several human diseases. Various hypotheses have been put forward to explain the evolution of genomic imprinting, but there is not yet a widely accepted general hypothesis for the variety of imprinting patterns observed. Here a new evolutionary hypothesis, based on intralocus sexual conflict, is proposed. This hypothesis provides a potential explanation for much of the currently available empirical data, and it also makes new predictions about patterns of genomic imprinting that are expected to evolve but that have not, as of yet, been looked for in nature. This theory also provides a potential mechanism for the resolution of intralocus sexual conflict in sexually selected traits and a novel pathway for the evolution of sexual dimorphism.     

Inbreeding,maternal care and genomic imprinting

Inactivation of expression of the paternal allele at two maternally silent imprinted loci has recently been reported to diminish the quality of care that female mice lavish on their offspring. This suggests that there can be disagreement between the maternally and paternally derived genomes of mothers over how much care for offspring is appropriate, with the paternally derived genome favoring greater care. The reason for such disagreement is not obvious because the maternally and paternally derived alleles at a locus have equal probabilities of being transmitted to each of the mother's ova and, therefore, would appear to have equal interests in a mother's offspring. However, if a female mates with a related male, her two alleles may have different probabilities of being present in the sperm that fertilize her ova. Natural selection can favor silencing of the maternally derived allele at a locus that enhances the quality of maternal care if the average patrilineal relatedness between a female and her mates decreases more rapidly than the average matrilineal relatedness. Just such an asymmetrical decrease in relatedness over time would be expected in a structured population in which patrilineal inbreeding is more common than matrilineal inbreeding.     

The continuing quest to comprehend genomic imprinting

The discovery of the phenomenon of genomic imprinting in mammals showed that the parental genomes are functionally non-equivalent. Considerable advances have occurred in the field over the past 20 years, which has resulted in the identification and functional analysis of a number of imprinted genes the expression of which is determined by their parental origin. These genes belong to many diverse categories and they have been shown to regulate growth, complex aspects of mammalian physiology and behavior. Many aspects of the mechanism of imprinting have also been elucidated. However, the reasons for the evolution of genomic imprinting remain enigmatic. Further research is needed to determine if there is any relationship between the apparently diverse functions of imprinted genes in mammals, and their role in human diseases. It also remains to be seen what common features exist amongst the diverse imprinting control elements. The mechanisms involved in the erasure and re-establishment of imprints should provide deeper insights into epigenetic mechanisms of wide general interest.     

Parental antagonism,relatedness asymmetries,and genomic imprinting.

The theory of inclusive fitness can be modified to consider separate coefficients of relatedness for an individual''s maternal and paternal alleles. A gene is said to have parentally antagonistic effects if it has an inclusive fitness benefit when maternally derived, but an inclusive fitness cost when paternally derived (or vice versa). Parental antagonism favours the evolution of alleles that are expressed only when maternally derived or only when paternally derived (genomic imprinting).     

Chromatin regulators of genomic imprinting

Genomic imprinting is an epigenetic phenomenon in which genes are expressed monoallelically in a parent-of-origin-specific manner. Each chromosome is imprinted with its parental identity. Here we will discuss the nature of this imprinting mark. DNA methylation has a well-established central role in imprinting, and the details of DNA methylation dynamics and the mechanisms that target it to imprinted loci are areas of active investigation. However, there is increasing evidence that DNA methylation is not solely responsible for imprinted expression. At the same time, there is growing appreciation for the contributions of post-translational histone modifications to the regulation of imprinting. The integration of our understanding of these two mechanisms is an important goal for the future of the imprinting field. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development.     

Competitive signal discrimination, methylation reprogramming and genomic imprinting

Genomic imprinting (parent-of-origin-dependent gene regulation) is associated with intra-genomic evolutionary conflict over the optimal pattern of gene expression. Most theoretical models of imprinting focus on the conflict between the maternally and paternally derived alleles at an imprinted locus. Recently, however, more attention has been focused on multi-directional conflicts involving not only the imprinted gene itself, but also the genes that encode the regulatory machinery responsible for establishing and maintaining imprinted gene expression. In this paper, I examine the conflict involved in epigenetic reprogramming of imprinted genes in early mammalian embryonic development. In the earliest phase of development, maternal-store proteins are responsible for most regulatory activity in the embryo. These proteins are under selection to maximize the mother's inclusive fitness, which is not identical to that of either of the sets of genes present in the embryo. Both the maternally and paternally derived genomes in the embryo favor maintenance of the epigenetic modifications established in the female and male germlines, respectively. Maternal-store proteins favor maintenance of some of these modifications, but erasure of others. Here I consider the logical structure of the machinery responsible for these two activities. Methylation maintenance is most effectively performed by AND-linked architectures, which may explain the unusual trafficking behavior of the oocyte-specific DNA methyltransferase, Dnmt1o. By contrast, demethylation is better supported by OR-linked architectures, which may explain the difficulty in identifying the factor(s) responsible for the active demethylation of the paternal genome following fertilization.