Perspective: maternal kin groups and the origins of asymmetric genetic systems-genomic imprinting, haplodiploidy, and parthenogenesis

The genetic systems of animals and plants are typically eumendelian. That is, an equal complement of autosomes is inherited from each of two parents, and at each locus, each parent's allele is equally likely to be expressed and equally likely to be transmitted. Genetic systems that violate any of these eumendelian symmetries are termed asymmetric and include parent-specific gene expression (PSGE), haplodiploidy, thelytoky, and related systems. Asymmetric genetic systems typically arise in lineages with close associations between kin (gregarious siblings, brooding, or viviparity). To date, different explanatory frameworks have been proposed to account for each of the different asymmetric genetic systems. Haig's kinship theory of genomic imprinting argues that PSGE arises when kinship asymmetries between interacting kin create conflicts between maternally and paternally derived alleles. Greater maternal than paternal relatedness within groups selects for more "abstemious" expression of maternally derived alleles and more "greedy" expression of paternally derived alleles. Here, I argue that this process may also underlie origins of haplodiploidy and many origins of thelytoky. The tendency for paternal alleles to be more "greedy" in maternal kin groups means that maternal-paternal conflict is not a zero-sum game: the maternal optimum will more closely correspond to the optimum for family groups and demes and for associated entities such as symbionts. Often in these circumstances, partial or complete suppression of paternal gene expression will evolve (haplodiploidy, thelytoky), or other features of the life cycle will evolve to minimize the conflict (monogamy, inbreeding). Maternally transmitted cytoplasmic elements and maternally imprinted nuclear alleles have a shared interest in minimizing agonistic interactions between female siblings and may cooperate to exclude the paternal genome. Eusociality is the most dramatic expression of the conflict-reducing effects of haplodiploidy, but its original and more widespread function may be suppression of intrafamilial cannibalism. In rare circumstances in which paternal gene products gain access to maternal physiology via a placenta, PSGE with greedy paternal gene expression can persist (e.g., in mammals).     

Genomic imprinting, sibling solidairity and the logic of collective action

Genomic imprinting has been proposed to evolve when a gene's expression has fitness consequences for individuals with different coefficients of matrilineal and patrilineal relatedness, especially in the context of competition between offspring for maternal resources. Previous models have focused on pre-emptive hierarchies, where conflict arises with respect to resource allocation between present and future offspring. Here we present a model in which imprinting arises from scramble competition within litters. The model predicts paternal-specific expression of a gene that increases an offspring's fractional share of resources but reduces the size of the resource pool, and maternal-specific expression of a gene with opposite effects. These predictions parallel the observation in economic models that individuals tend to underprovide public goods, and that the magnitude of this shortfall increases with the number of individuals in the group. Maternally derived alleles are more willing than their paternally derived counterparts to contribute to public goods because they have a smaller effective group size.     

Parental modifiers,antisense transcripts and loss of imprinting

The kinship theory of genomic imprinting has explained parent-specific gene expression as the outcome of an evolutionary conflict between the two alleles at a diploid locus of an offspring over how much to demand from parents. Previous models have predicted that maternally derived (madumnal) alleles will be silent at demand-enhancing loci, while paternally derived (padumnal) alleles will be silent at demand-suppressing loci, but these models have not considered the evolution of trans-acting modifiers that are expressed in parents and influence imprinted expression in offspring. We show that such modifiers will sometimes be selected to reactivate the silent padumnal allele at a demand-suppressing locus but will not be selected to reactivate the silent madumnal allele at a demand-enhancing locus. Therefore, imprinting of demand-suppressing loci is predicted to be less evolutionarily stable than imprinting of demand-enhancing loci.     

Transitional hemizygosity of the maternally derived allele at the 6PGD locus during early development of the Cyprinid fish Rutilus rutilus

The activation of individual alleles during early embryogenesis was studied at the 6-phosphogluconate dehydrogenase gene locus of the Cyprinid fish Rutilus by means of starch gel electrophoresis. By using three alleles occurring at this locus, it was possible to discriminate between (1) maternally transmitted gene products stored in the egg cytoplasm, (2) newly synthesized protein of the maternally derived allele in the embryonic genome, and (3) newly synthesized protein of the paternally derived allele. It was found that, until the fifth day of development, maternal products were present in the embryo. By the seventh day after fertilization, these storage products were nearly exhausted, and a hemizygous phenotype for the maternally derived gene became visible. On the eighth day, the patterns of all four allelic combinations of the mating type used were demonstrable in the offspring. The findings suggest that for the alleles used in this study, the maternally derived gene is preferentially activated during embryogenesis.Supported by the Deutsche Forschungsgemeinschaft.     

Synchronous activation of both parental alleles at the 6-PGD locus of Japanese quail embryos

The gene locus for the enzyme 6-phosphogluconate dehydrogenase belongs to that part of the genome which is activated at the beginning of embryonic development. The present experiment, utilizing three alleles at this autosomally inherited locus of the Japanese quail, was designed to show whether exhaustion of maternally stored 6-PGD is followed by maternally hemizygous de novo synthesis of the same enzyme. 6-PGD phenotypes of early embryos resulting from the mating between a male homozygous for one allele and a female heterozygous for two other alleles were examined by starch gel electrophoresis. The result showed that the maternally stored 6-PGD is exhausted before the twenty-fourth hour of incubation. This is followed by synchronous activation of both parental alleles. Previous studies on the development of various interspecific crosses have revealed that, at all loci studied, the activation of the maternally derived allele preceded that of the paternally derived allele. The present experiment reveals that preferential activation of maternally derived alleles need not be a rule of development.This work was supported in part by a grant (CA-05138) from the National Cancer Institute, U.S. Public Health Service, and in part by a research fund established in honor of General James H. Doolittle. Contribution No. 6-68, Department of Biology, City of Hope Medical Center.     

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.     

Assessment of parent-of-origin effects in linkage analysis of quantitative traits

Methods are presented for incorporation of parent-of-origin effects into linkage analysis of quantitative traits. The estimated proportion of marker alleles shared identical by descent is first partitioned into a component derived from the mother and a component derived from the father. These parent-specific estimates of allele sharing are used in variance-components or Haseman-Elston methods of linkage analysis so that the effect of the quantitative-trait locus carried on the maternally derived chromosome is potentially different from the effect of the locus on the paternally derived chromosome. Statistics for linkage between trait and marker loci derived from either or both parents are then calculated, as are statistics for testing whether the effect of the maternally derived locus is equal to that of the paternally derived locus. Analyses of data simulated for 956 siblings from 263 nuclear families who had participated in a linkage study revealed that type I error rates for these statistics were generally similar to nominal values. Power to detect an imprinted locus was substantially increased when analyzed with a model allowing for parent-of-origin effects, compared with analyses that assumed equal effects; for example, for an imprinted locus accounting for 30% of the phenotypic variance, the expected LOD score was 4.5 when parent-of-origin effects were incorporated into the analysis, compared with 3.1 when these effects were ignored. The ability to include parent-of-origin effects within linkage analysis of quantitative traits will facilitate genetic dissection of complex traits.     

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).     

Avoidance of close consanguineous inbreeding in captive groups of rhesus macaques

In three captive groups of rhesus macaques (Macaca mulatto) the intensity of inbreeding avoidance was directly correlated with the closeness of kinship. The incidence of inbreeding between matrilineal relatives was lower than expected were mating to occur randomly with regard to matrilineal affiliation. The avoidance of mating between sons and their mothers and between matrilineal sibs contributed about squally to this outcome. The incidence of mating between more remote matrilineal relatives was lower than, but could not be shown to differ significantly from, that expected at the 0.05 level of probability. Familiarity fostered by interactions among matriline members probably provides a focus for avoidance of matrilineal inbreeding, and might influence male dispersal. Results of this study are consistent with reports of female rhesus macaques' avoidance of sexual activity with matrilineal male relatives as predicted by parental investment theory The observed incidence of inbreeding between patrilineal relatives was not different from that expected, but significantly fewer of the patrilineally inbred matings involved father/daughter matings than expected were mating random. Recognition of phenotypic similarities might provide a focus for avoidance of inbreeding between fathers and their daughters, but is loss reliable than strategies for avoiding matrilineal inbreeding. Adaptations for avoiding matrilineal inbreeding that are more effective than those for avoiding patrilineal inbreeding might have evolved because the risk of patrilineal inbreeding, and hence the resulting loss in fitness, is marginal compared to that for matrilineal inbreeding in free-ranging groups. © 1995 Wiley-Liss, Inc.     

Polyandry, life-history trade-offs and the evolution of imprinting at Mendelian loci

Genomic imprinting causes parental origin-dependent differential expression of a small number of genes in mammalian and angiosperm plant embryos, resulting in non-Mendelian inheritance of phenotypic traits. The "conflict" theory of the evolution of imprinting proposes that reduced genetic relatedness of paternally, relative to maternally, derived alleles in offspring of polygamous females supports parental sex-specific selection at gene loci that influence maternal investment. While the theory's physiological predictions are well supported by observation, the requirement of polyandry in the evolution of imprinting from an ancestral Mendelian state has not been comprehensively analyzed. Here, we use diallelic models to examine the influence of various degrees of polyandry on the evolution of both Mendelian and imprinted autosomal gene loci that influence trade-offs between maternal fecundity and offspring viability. We show that, given a plausible assumption on the physiological relationship between maternal fecundity and offspring viability, low levels of polyandry are sufficient to reinforce exclusively the fixation of "greedy" paternally imprinted alleles that increase offspring viability at the expense of maternal fecundity and "thrifty" maternally imprinted alleles of opposite effect. We also show that, for all levels of polyandry, Mendelian alleles at genetic loci that influence the trade-off between maternal fecundity and offspring viability reach an evolutionary stable state, whereas pairs of reciprocally imprinted alleles do not.     

Female choice and the relatedness of mates in the guppy (<Emphasis Type="Italic">Poecilia reticulata</Emphasis>)

Several studies suggest that females may offset the costs of genetic incompatibility by exercising pre-copulatory or post-copulatory mate choice to bias paternity toward more compatible males. One source of genetic incompatibility is the degree of relatedness among mates; unrelated males are expected to be genetically more compatible with a female than her relatives. To address this idea, we investigated the potential for inbreeding depression and paternity biasing mechanisms (pre- and post-copulatory) of inbreeding avoidance in the guppy, Poecilia reticulata. Inbreeding resulted in a reduction in offspring number and quality. Females mated to siblings gave birth to significantly fewer offspring compared to females mated to non-siblings and inbred male offspring took longer to reach sexual maturity. There was no evidence of inbreeding avoidance in pre-copulatory behaviors of females or males. Sexual responsiveness of females to courting males and the number of sexual behaviors males directed at females did not decrease as a function of the relatedness of the two individuals. We also tested whether female guppies can use post-copulatory mechanisms to bias sperm usage toward unrelated males by comparing the number of offspring produced by females mated to two of their siblings (SS), two males unrelated to the female (NN), or to one unrelated male and a sibling male (NS). We found that NS females produced a number of offspring not significantly different than what would be expected if fertilization success were halfway between completely outbreeding (NN) and completely inbreeding (SS) females. This suggests that there is no significant improvement in the number of offspring produced by females mating to both related and unrelated males, relative to that which would be expected if sperm from both males were used equally. Our results suggest that female guppies do not discriminate against closely related males or their sperm.     

Genomic imprinting and kinship in the social Hymenoptera: what are the predictions?

The kinship theory of genomic imprinting predicts that conflicts of interest between parents can promote the evolution of opposed expression patterns of maternally and paternally derived alleles in the offspring. The social Hymenoptera (ants, some bees, and some wasps) are particularly suitable to test this theory, because a variety of social conflicts are predicted due to relatedness asymmetries between female and male nestmates that are a corollary of haplo-diploid sex determination. Here I argue that the kin-selection predictions for genomic imprinting in social Hymenoptera might in many cases be more complex than previously suggested, because the optimal strategy will have to take fitness effects in different castes and sexes into account.     

What Happens after Inbreeding Avoidance? Inbreeding by Rejected Relatives and the Inclusive Fitness Benefit of Inbreeding Avoidance

Avoiding inbreeding, and therefore avoiding inbreeding depression in offspring fitness, is widely assumed to be adaptive in systems with biparental reproduction. However, inbreeding can also confer an inclusive fitness benefit stemming from increased relatedness between parents and inbred offspring. Whether or not inbreeding or avoiding inbreeding is adaptive therefore depends on a balance between inbreeding depression and increased parent-offspring relatedness. Existing models of biparental inbreeding predict threshold values of inbreeding depression above which males and females should avoid inbreeding, and predict sexual conflict over inbreeding because these thresholds diverge. However, these models implicitly assume that if a focal individual avoids inbreeding, then both it and its rejected relative will subsequently outbreed. We show that relaxing this assumption of reciprocal outbreeding, and the assumption that focal individuals are themselves outbred, can substantially alter the predicted thresholds for inbreeding avoidance for focal males. Specifically, the magnitude of inbreeding depression below which inbreeding increases a focal male’s inclusive fitness increases with increasing depression in the offspring of a focal female and her alternative mate, and it decreases with increasing relatedness between a focal male and a focal female’s alternative mate, thereby altering the predicted zone of sexual conflict. Furthermore, a focal male’s inclusive fitness gain from avoiding inbreeding is reduced by indirect opportunity costs if his rejected relative breeds with another relative of his. By demonstrating that variation in relatedness and inbreeding can affect intra- and inter-sexual conflict over inbreeding, our models lead to novel predictions for family dynamics. Specifically, parent-offspring conflict over inbreeding might depend on the alternative mates of rejected relatives, and male-male competition over inbreeding might lead to mixed inbreeding strategies. Making testable quantitative predictions regarding inbreeding strategies occurring in nature will therefore require new models that explicitly capture variation in relatedness and inbreeding among interacting population members.     

Sperm selection and genetic incompatibility: does relatedness of mates affect male success in sperm competition?

Sperm selection may be said to occur if females influence the relative success of ejaculates competing to fertilize their ova. Most evidence that female animals or their ova are capable of sperm selection relates to male genetic incompatibility, although relatively few studies focus on competition between conspecific males. Here I look for evidence of sperm selection with respect to relatedness of mates. Reduced fitness or inbreeding effects in offspring resulting from copulations between close relatives are well documented. If females are capable of sperm selection, they might therefore be expected to discriminate against the sperm of sibling males during sperm competition. I describe an experimental protocol designed to test for evidence of sperm selection while controlling for inbreeding effects. Using decorated field crickets (Gryllodes supplicans), I found that sibling males achieved lower fertilization success in competition with a male unrelated to the female than in competition with another sibling more frequently than expected by chance, although the mean paternity values did not differ significantly between treatments. The tendancy for sibling males to achieve relatively lower fertilization success in competition with males unrelated to the female could not be explained by the effects of increased ejaculate allocation, female control of sperm transfer or inbreeding. This study therefore provides some evidence in support of the idea that female insects (or their ova) may be capable of selection against sperm on the basis of genetic similarity of conspecific males.     

A fine analysis of glucose-phosphate-isomerase patterns in single preimplantation mouse embryos

Mouse embryos were derived from eggs heterozygous for alleles of the dimeric enzyme glucose phosphate isomerase (Gpi-1a/Gpi-1b) that had been fertilized with sperm carrying a third allele (Gpi-1c). This particular combination makes it possible to study the activity of the paternally derived as well as the maternally derived genes, the persistence of oocyte-coded enzyme throughout early development and the possible simultaneous expression of both the paternally derived allele and the maternal message. The different isozymes present in single embryos were separated by electrophoresis. The results show that the oocyte-coded glucose phosphate isomerase is gradually replaced by embryo-coded enzyme. Expression of the paternally derived allele was first detected at the morula stage, during which the translation of the maternally derived message seemed to be either exhausted or below the detection limit of our system. Some oocyte-coded enzyme persisted until after implantation.     

X-linked gene expression in metatherian fibroblasts: Evidence from theGpd andPgk-A loci of the Virginia opossum and the red-necked wallaby

Fibroblasts cultured from ear pinna biopsies of Virginia opossums (Didelphis virginiana) and red-necked wallabies (Macropus rufogriseus) were examined electrophoretically to determine the relative expression levels of the maternally and paternally derived alleles at X-linked, enzyme-coding loci. Only the maternally derived allele was expressed at thePgk-A locus in fibroblasts of heterozygousD. virginiana (M. rufogriseus not examined), but fibroblasts of both species exhibited evidence of paternal allele expression a t theGpd locus. Furthermore, the heterozygous G6PD phenotypes in both species were skewed in favor of the maternal gene product, as expected if the paternal allele is only partially (incompletely) expressed. ForM. rufogriseus this result is contrary to a previous finding which suggested equal expression of bothGpd alleles in cultured fibroblasts of this species. The present results suggest that X-linked genes in metatherian fibroblasts are subject to the same kind of determinate, paternal allele inactivation, incomplete at some loci, described previously for X-linked genes in adult tissues and that the pattern of paternal X-linked gene expression in these cells is independent of the patterns in the tissues from which the fibroblasts are derived.The work was supported in part by grants from the National Institutes of Health (Biomedical Research Support Grant RR-05519) and the National Science Foundation (DCB 8516949).     

Transmission-Ratio Distortion through F(1) Females at Chromosome 11 Loci Linked to Om in the Mouse Ddk Syndrome

We determined the genotypes of >200 offspring that are survivors of matings between female reciprocal F(1) hybrids (between the DDK and C57BL/6J inbred mouse strains) and C57BL/6J males at markers linked to the Ovum mutant (Om) locus on chromosome 11. In contrast to the expectations of our previous genetic model to explain the ``DDK syndrome,' the genotypes of these offspring do not reflect preferential survival of individuals that receive C57BL/6J alleles from the F(1) females in the region of chromosome 11 to which the Om locus has been mapped. In fact, we observe significant transmission-ratio distortion in favor of DDK alleles in this region. These results are also in contrast to the expectations of Wakasugi's genetic model for the inheritance of Om, in which he proposed equal transmission of DDK and non-DDK alleles from F(1) females. We propose that the results of these experiments may be explained by reduced expression of the maternal DDK Om allele or expression of the maternal DDK Om allele in only a portion of the ova of F(1) females.     

Female mating preferences and offspring survival: testing hypotheses on the genetic basis of mate choice in a wild lekking bird

Indirect benefits of mate choice result from increased offspring genetic quality and may be important drivers of female behaviour. ‘Good‐genes‐for‐viability’ models predict that females prefer mates of high additive genetic value, such that offspring survival should correlate with male attractiveness. Mate choice may also vary with genetic diversity (e.g. heterozygosity) or compatibility (e.g. relatedness), where the female's genotype influences choice. The relative importance of these nonexclusive hypotheses remains unclear. Leks offer an excellent opportunity to test their predictions, because lekking males provide no material benefits and choice is relatively unconstrained by social limitations. Using 12 years of data on lekking lance‐tailed manakins, Chiroxiphia lanceolata, we tested whether offspring survival correlated with patterns of mate choice. Offspring recruitment weakly increased with father attractiveness (measured as reproductive success, RS), suggesting attractive males provide, if anything, only minor benefits via offspring viability. Both male RS and offspring survival until fledging increased with male heterozygosity. However, despite parent–offspring correlation in heterozygosity, offspring survival was unrelated to its own or maternal heterozygosity or to parental relatedness, suggesting survival was not enhanced by heterozygosity per se. Instead, offspring survival benefits may reflect inheritance of specific alleles or nongenetic effects. Although inbreeding depression in male RS should select for inbreeding avoidance, mates were not less related than expected under random mating. Although mate heterozygosity and relatedness were correlated, selection on mate choice for heterozygosity appeared stronger than that for relatedness and may be the primary mechanism maintaining genetic variation in this system despite directional sexual selection.     

Gene activation of alcohol dehydrogenase in danio hybrids

The regulation of alleles encoding the enzyme alcohol dehydrogenase (ADH) was investigated in F1Brachydanio hybrids (zebra danio female x spotted danio male) by acrylamide gel electrophoresis. Both parental species showed a single, cathodal band of species-specific ADH. During development at 26 degrees C, hybrid fry showed a preferential activation of the maternally derived Adh allele. It is suggested that the low activity of the paternally derived allele may result from an incompatibility between maternal regulatory factors and the paternal regulative element controlling gene expression.     

No evidence of inbreeding avoidance or inbreeding depression in a social carnivore

Dispersal by young mammals away from their natal site is generallythought to reduce inbreeding, with its attendant negative fitnessconsequences. Genetic data from the dwarf mongoose, a pack-livingcarnivore common in African savannas, indicate that there areexceptions to this generalization. In dwarf mongoose populationsin the Serengeti National Park, Tanzania, breeding pairs arecommonly related, and close inbreeding has no measurable effecton offspring production or adult survival. Inbreeding occursbecause average relatedness among potential mates within a packis high, because mating patterns within the pack are randomwith respect to the relatedness of mates, and because dispersaldoes little to decrease the relatedness among mates. Young femalesare more likely to leave a pack when the dominant male is aclose relative but are relatively infrequent dispersers. Youngmales emigrate at random with respect to the relatedness ofthe dominant female and tend to disperse to packs that containgenetically similar individuals.[Behav Ecol 7: 480–489(1996)]