The Relationship between Sexual Selection and Sexual Conflict

Evolutionary conflicts of interest arise whenever genetically different individuals interact and their routes to fitness maximization differ. Sexual selection favors traits that increase an individual’s competitiveness to acquire mates and fertilizations. Sexual conflict occurs if an individual of sex A’s relative fitness would increase if it had a “tool” that could alter what an individual of sex B does (including the parental genes transferred), at a cost to B’s fitness. This definition clarifies several issues: Conflict is very common and, although it extends outside traits under sexual selection, sexual selection is a ready source of sexual conflict. Sexual conflict and sexual selection should not be presented as alternative explanations for trait evolution. Conflict is closely linked to the concept of a lag load, which is context-dependent and sex-specific. This makes it possible to ask if one sex can “win.” We expect higher population fitness if females win.Many published studies ask if sexual selection or sexual conflict drives the evolution of key reproductive traits (e.g., mate choice). Here we argue that this is an inappropriate question. By analogy, G. Evelyn Hutchinson (1965) coined the phrase “the ecological theatre and the evolutionary play” to capture how factors that influence the birth, death, and reproduction of individuals (studied by ecologists) determine which individuals reproduce, and “sets the stage” for the selective forces that drive evolutionary trajectories (studied by evolutionary biologists). The more modern concept of “eco-evolutionary feedback” (Schoener 2011) emphasizes that selection changes the character of the actors over time, altering their ecological interactions. No one would sensibly ask whether one or the other shapes the natural world, when obviously both interact to determine the outcome.So why have sexual conflict and sexual selection sometimes been elevated to alternate explanations? This approach is often associated with an assumption that sexual conflict affects traits under direct selection, favoring traits that alter the likelihood of a potential mate agreeing or refusing to mate because it affects the bearer’s immediate reproductive output, whereas “traditional” sexual selection is assumed to favor traits that are under indirect selection because they increase offspring fitness. These “traditional” models are sometimes described as “mutualistic” (e.g., Pizzari and Snook 2003; Rice et al. 2006), although this term appears to be used only when contrasting them with sexual conflict models. The investigators of the original models never describe them as “mutualistic,” which is hardly surprising given that some males are rejected by females.In this review, we first define sexual conflict and sexual selection. We then describe how the notion of a “lag load” can reveal which sex currently has greater “power” in a sexual conflict over a specific resource. Next, we discuss why sexual conflict and sexual selection are sometimes implicitly (or explicitly) presented as alternative explanations for sexual traits (usually female mate choice/resistance). To illustrate the problems with the assumptions made to take this stance, we present a “toy model” of snake mating behavior based on a study by Shine et al. (2005). We show that empirical predictions about the mating behavior that will be observed if females seek to minimize direct cost of mating or to obtain indirect genetic benefits were overly simplistic. This allows us to make the wider point that whom a female is willing to mate with and how often she mates are often related questions. Finally, we discuss the effect of sexual conflict on population fitness.     

Antagonistic Parent-Offspring Co-Adaptation

Background

In species across taxa, offspring have means to influence parental investment (PI). PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.

Methodology/Principal Findings

In contrast to previous theory that largely uses a static approach to predict how “offspring individuals” and “parental individuals” should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.

Conclusions/Significance

We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.     

Sexually Antagonistic “Zygotic Drive” of the Sex Chromosomes

Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic “zygotic drive”, because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic “arms race” between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.     

Experimental evidence for adaptive personalities in a wild passerine bird

Individuals of the same species differ consistently in risky actions. Such ‘animal personality’ variation is intriguing because behavioural flexibility is often assumed to be the norm. Recent theory predicts that between-individual differences in propensity to take risks should evolve if individuals differ in future fitness expectations: individuals with high long-term fitness expectations (i.e. that have much to lose) should behave consistently more cautious than individuals with lower expectations. Consequently, any manipulation of future fitness expectations should result in within-individual changes in risky behaviour in the direction predicted by this adaptive theory. We tested this prediction and confirmed experimentally that individuals indeed adjust their ‘exploration behaviour’, a proxy for risk-taking behaviour, to their future fitness expectations. We show for wild great tits (Parus major) that individuals with experimentally decreased survival probability become faster explorers (i.e. increase risk-taking behaviour) compared to individuals with increased survival probability. We also show, using quantitative genetics approaches, that non-genetic effects (i.e. permanent environment effects) underpin adaptive personality variation in this species. This study thereby confirms a key prediction of adaptive personality theory based on life-history trade-offs, and implies that selection may indeed favour the evolution of personalities in situations where individuals differ in future fitness expectations.     

Fitness Benefits of Mate Choice for Compatibility in a Socially Monogamous Species

Research on mate choice has primarily focused on preferences for quality indicators, assuming that all individuals show consensus about who is the most attractive. However, in some species, mating preferences seem largely individual-specific, suggesting that they might target genetic or behavioral compatibility. Few studies have quantified the fitness consequences of allowing versus preventing such idiosyncratic mate choice. Here, we report on an experiment that controls for variation in overall partner quality and show that zebra finch (Taeniopygia guttata) pairs that resulted from free mate choice achieved a 37% higher reproductive success than pairs that were forced to mate. Cross-fostering of freshly laid eggs showed that embryo mortality (before hatching) primarily depended on the identity of the genetic parents, whereas offspring mortality during the rearing period depended on foster-parent identity. Therefore, preventing mate choice should lead to an increase in embryo mortality if mate choice targets genetic compatibility (for embryo viability), and to an increase in offspring mortality if mate choice targets behavioral compatibility (for better rearing). We found that pairs from both treatments showed equal rates of embryo mortality, but chosen pairs were better at raising offspring. These results thus support the behavioral, but not the genetic, compatibility hypothesis. Further exploratory analyses reveal several differences in behavior and fitness components between “free-choice” and “forced” pairs.     

THE EVOLUTION OF MATERNAL CHARACTERS

We develop quantitative-genetic models for the evolution of multiple traits under maternal inheritance, in which traits are transmitted through non-Mendelian as well as Mendelian mechanisms, and maternal selection, in which the fitness of offspring depends on their mother's phenotype as well as their own. Maternal inheritance results in time lags in the evolutionary response to selection. These cause a population to evolve for an indefinite number of generations after selection ceases and make the rate and direction of evolution change even when the strength of selection and parameters of inheritance remain constant. The rate and direction of evolution depend on the inheritance of traits that are not under selection, unlike under classical Mendelian inheritance. The models confirm earlier findings that the response to selection can be larger or smaller than what is possible with simple Mendelian inheritance, and even in a direction opposite to what selection favors. Maternal selection, in which a mother's phenotype influences her offspring's fitness, is frequency-dependent and can cause a population to evolve maladaptively away from a fitness peak, regardless of whether traits are transmitted by Mendelian or maternal inheritance. Maternal selection differs from other forms of selection in that its force depends not only on the fitness function but also on the phenotypic resemblance of parents and offspring.     

Plastics Derived Endocrine Disruptors (BPA,DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity,Reproductive Disease and Sperm Epimutations

Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.     

Does egg carotenoid improve larval quality in Arctic charr (Salvelinus alpinus)?

Females in mutually ornamented species are often less conspicuously ornamented than their male conspecifics. It has been hypothesized that offspring quality may decrease if females invest more resources into ornaments at the expense of resources in eggs. An experiment was carried out to test whether natural variation in carotenoid in the eggs from a wild population of Arctic charr (Salvelinus alpinus) was associated with survival and growth of their offspring until hatching. Wild Arctic charr were caught at a spawning ground during the spawning period. Eggs from two different females, one female with yellowish carotenoid‐rich eggs and one with paler eggs, were fertilized by sperm from the same male. This was repeated until gametes were collected from 42 females and 21 males, giving a total of 21 groups. After fertilization, the zygotes from each of the two females were reared in four replicated groups. These 168 groups were reared separately until hatching when the surviving larvae were counted and their body length measured. For the two response variables survival and body length at hatching, no effect was demonstrated of any of the predictors (i) amount of carotenoid in the unfertilized eggs, (ii) the mothers'' body condition, or (iii) ornament intensity of their red carotenoid‐based abdominal ornament. Thus, this study gives no support for the hypothesis that females investing less carotenoid into their eggs suffer from decreased offspring quality until hatching. This lack of association between female ornament intensity and their fitness is not as expected if female ornaments evolved due to direct sexual selection from males on the more ornamented females (“direct selection hypothesis”).     

Immune-mediated change in the expression of a sexual trait predicts offspring survival in the wild

Background

The “good genes” theory of sexual selection postulates that females choose mates that will improve their offspring''s fitness through the inheritance of paternal genes. In spite of the attention that this hypothesis has given rise to, the empirical evidence remains sparse, mostly because of the difficulties of controlling for the many environmental factors that may covary with both the paternal phenotype and offspring fitness. Here, we tested the hypothesis that offspring sired by males of a preferred phenotype should have better survival in an endangered bird, the houbara bustard (Chlamydotis undulata undulata).

Methodology/Principal Findings

We tested if natural and experimentally-induced variation in courtship display (following an inflammatory challenge) predicts the survival of offspring. Chicks were produced by artificial insemination of females, ensuring that any effect on survival could only arise from the transfer of paternal genes. One hundred and twenty offspring were equipped with radio transmitters, and their survival monitored in the wild for a year. This allowed assessment of the potential benefits of paternal genes in a natural setting, where birds experience the whole range of environmental hazards. Although natural variation in sire courtship display did not predict offspring survival, sires that withstood the inflammatory insult and maintained their courtship activity sired offspring with the best survival upon release.

Conclusions

This finding is relevant both to enlighten the debate on “good genes” sexual selection and the management of supportive breeding programs.     

Costs of Rearing the Wrong Sex: Cross-Fostering to Manipulate Offspring Sex in Tammar Wallabies

Sex allocation theory assumes that offspring sex (son vs. daughter) has consequences for maternal fitness. The most compelling experiment to test this theory would involve manipulating offspring sex and measuring the fitness consequences of having the “wrong” sex. Unfortunately, the logistical challenges of such an experiment limit its application. In tammar wallabies (Macropus eugenii), previous evidence suggests that mothers in good body condition are more likely to produce sons compared to mothers in poor condition, in support of the Trivers-Willard Hypothesis (TW) of condition-dependent sex allocation. More recently, we have found in our population of tammar wallabies that females with seemingly poor access to resources (based on condition loss over the dry summer) are more likely to produce sons, consistent with predictions from the Local Resource Competition (LRC) hypothesis, which proposes that production of sons or daughters is driven by the level of potential competition between mothers and philopatric daughters. We conducted a cross-fostering experiment in free-ranging tammar wallabies to disassociate the effects of rearing and birthing offspring of each sex. This allowed us to test the prediction of the LRC hypothesis that rearing daughters reduces the future direct fitness of mothers post-weaning and the prediction of the TW hypothesis that rearing sons requires more energy during lactation. Overall, we found limited costs to the mother of rearing the “wrong” sex, with switching of offspring sex only reducing the likelihood of a mother having a pouch young the following year. Thus, we found some support for both hypotheses in that rearing an unexpected son or an unexpected daughter both lead to reduced future maternal fitness. The study suggests that there may be context-specific costs associated with rearing the “wrong” sex.     

Many chronological aging clocks can be found throughout the epigenome: Implications for quantifying biological aging

Epigenetic alterations are a hallmark of aging and age‐related diseases. Computational models using DNA methylation data can create “epigenetic clocks” which are proposed to reflect “biological” aging. Thus, it is important to understand the relationship between predictive clock sites and aging biology. To do this, we examined over 450,000 methylation sites from 9,699 samples. We found ~20% of the measured genomic cytosines can be used to make many different epigenetic clocks whose age prediction performance surpasses that of telomere length. Of these predictive sites, the average methylation change over a lifetime was small (~1.5%) and these sites were under‐represented in canonical regions of epigenetic regulation. There was only a weak association between “accelerated” epigenetic aging and disease. We also compare tissue‐specific and pan‐tissue clock performance. This is critical to applying clocks both to new sample sets in basic research, as well as understanding if clinically available tissues will be feasible samples to evaluate “epigenetic aging” in unavailable tissues (e.g., brain). Despite the reproducible and accurate age predictions from DNA methylation data, these findings suggest they may have limited utility as currently designed in understanding the molecular biology of aging and may not be suitable as surrogate endpoints in studies of anti‐aging interventions. Purpose‐built clocks for specific tissues age ranges or phenotypes may perform better for their specific purpose. However, if purpose‐built clocks are necessary for meaningful predictions, then the utility of clocks and their application in the field needs to be considered in that context.     

Genetic Diversity in the Interference Selection Limit

Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasingly severe as the density of selected polymorphisms increases. Here, we describe a simple limit that emerges when interference is common, in which the fitness effects of individual mutations play a relatively minor role. Instead, similar to models of quantitative genetics, molecular evolution is determined by the variance in fitness within the population, defined over an effectively asexual segment of the genome (a “linkage block”). We exploit this insensitivity in a new “coarse-grained” coalescent framework, which approximates the effects of many weakly selected mutations with a smaller number of strongly selected mutations that create the same variance in fitness. This approximation generates accurate and efficient predictions for silent site variability when interference is common. However, these results suggest that there is reduced power to resolve individual selection pressures when interference is sufficiently widespread, since a broad range of parameters possess nearly identical patterns of silent site variability.     

A Mixture of “Cheats” and “Co-Operators” Can Enable Maximal Group Benefit

Is a group best off if everyone co-operates? Theory often considers this to be so (e.g. the “conspiracy of doves”), this understanding underpinning social and economic policy. We observe, however, that after competition between “cheat” and “co-operator” strains of yeast, population fitness is maximized under co-existence. To address whether this might just be a peculiarity of our experimental system or a result with broader applicability, we assemble, benchmark, dissect, and test a systems model. This reveals the conditions necessary to recover the unexpected result. These are 3-fold: (a) that resources are used inefficiently when they are abundant, (b) that the amount of co-operation needed cannot be accurately assessed, and (c) the population is structured, such that co-operators receive more of the resource than the cheats. Relaxing any of the assumptions can lead to population fitness being maximized when cheats are absent, which we experimentally demonstrate. These three conditions will often be relevant, and hence in order to understand the trajectory of social interactions, understanding the dynamics of the efficiency of resource utilization and accuracy of information will be necessary.     

O-GlcNAc and the Epigenetic Regulation of Gene Expression

O-GlcNAcylation is an abundant nutrient-driven modification linked to cellular signaling and regulation of gene expression. Utilizing precursors derived from metabolic flux, O-GlcNAc functions as a homeostatic regulator. The enzymes of O-GlcNAc cycling, OGT and O-GlcNAcase, act in mitochondria, the cytoplasm, and the nucleus in association with epigenetic “writers” and “erasers” of the histone code. Both O-GlcNAc and O-phosphate modify repeats within the RNA polymerase II C-terminal domain (CTD). By communicating with the histone and CTD codes, O-GlcNAc cycling provides a link between cellular metabolic status and the epigenetic machinery. Thus, O-GlcNAcylation is poised to influence trans-generational epigenetic inheritance.     

Maternal inheritance,epigenetics and the evolution of polyandry

Growing evidence indicates that females actively engage in polyandry either to avoid genetic incompatibility or to bias paternity in favor of genetically superior males. Despite empirical support for the intrinsic male quality hypothesis, the maintenance of variation in male fitness remains a conundrum for traditional "good genes" models of sexual selection. Here, we discuss two mechanisms of non-Mendelian inheritance, maternal inheritance of mitochondria and epigenetic regulation of gene expression, which may explain the persistence of variation in male fitness traits important in post-copulatory sexual selection. The inability of males to transmit mitochondria precludes any direct evolutionary response to selection on mitochondrial mutations that reduce or enhance male fitness. Consequently, mitochondrial-based variation in sperm traits is likely to persist, even in the face of intense sperm competition. Indeed, mitochondrial nucleotide substitutions, deletions and insertions are now known to be a primary cause of low sperm count and poor sperm motility in humans. Paradoxically, in the field of sexual selection, female-limited response to selection has been largely overlooked. Similarly, the contribution of epigenetics (e.g., DNA methylation, histone modifications and non-coding RNAs) to heritable variation in male fitness has received little attention from evolutionary theorists. Unlike DNA sequence based variation, epigenetic variation can be strongly influenced by environmental and stochastic effects experienced during the lifetime of an individual. Remarkably, in some cases, acquired epigenetic changes can be stably transmitted to offspring. A recent study indicates that sperm exhibit particularly high levels of epigenetic variation both within and between individuals. We suggest that such epigenetic variation may have important implications for post-copulatory sexual selection and may account for recent findings linking sperm competitive ability to offspring fitness.     

Source-Sink Colonization as a Possible Strategy of Insects Living in Temporary Habitats

Continuous colonization and re-colonization is critical for survival of insect species living in temporary habitats. When insect populations in temporary habitats are depleted, some species may escape extinction by surviving in permanent, but less suitable habitats, in which long-term population survival can be maintained only by immigration from other populations. Such situation has been repeatedly described in nature, but conditions when and how this occurs and how important this phenomenon is for insect metapopulation survival are still poorly known, mainly because it is difficult to study experimentally. Therefore, we used a simulation model to investigate, how environmental stochasticity, growth rate and the incidence of dispersal affect the positive effect of permanent but poor (“sink”) habitats on the likelihood of metapopulation persistence in a network of high quality but temporary (“source”) habitats. This model revealed that permanent habitats substantially increase the probability of metapopulation persistence of insect species with poor dispersal ability if the availability of temporary habitats is spatio-temporally synchronized. Addition of permanent habitats to a system sometimes enabled metapopulation persistence even in cases in which the metapopulation would otherwise go extinct, especially for species with high growth rates. For insect species with low growth rates the probability of a metapopulation persistence strongly depended on the proportions of “source” to “source” and “sink” to “source” dispersal rates.     

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort

Background

A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7–8 years of life in a large Amsterdam born birth cohort.

Methods

For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes “ever being diagnosed with asthma” and “wheezing in the past 12 months” on questionnaires. We measured offspring height and weight at age 5–6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma.

Results

At the age of 7–8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49–3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28–3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma.

Conclusions

Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child’s own BMI.     

Kinship,dear enemies,and costly combat: The effects of relatedness on territorial overlap and aggression in a cooperative breeder

Many species maintain territories, but the degree of overlap between territories and the level of aggression displayed in territorial conflicts can vary widely, even within species. Greater territorial overlap may occur when neighboring territory holders are close relatives. Animals may also differentiate neighbors from strangers, with more familiar neighbors eliciting less‐aggressive responses during territorial conflicts (the “dear enemy” effect). However, research is lacking in how both kinship and overlap affect territorial conflicts, especially in group‐living species. Here, we investigate kinship, territorial overlap, and territorial conflict in a habituated wild population of group‐living cooperatively breeding birds, the southern pied babbler Turdoides bicolor. We find that close kin neighbors are beneficial. Territories overlap more when neighboring groups are close kin, and these larger overlaps with kin confer larger territories (an effect not seen for overlaps with unrelated groups). Overall, territorial conflict is costly, causing significant decreases in body mass, but conflicts with kin are shorter than those conducted with nonkin. Conflicts with more familiar unrelated neighbors are also shorter, indicating these neighbors are “dear enemies.” However, kinship modulates the “dear enemy” effect; even when kin are encountered less frequently, kin elicit less‐aggressive responses, similar to the “dear enemy” effect. Kin selection appears to be a main influence on territorial behavior in this species. Groups derive kin‐selected benefits from decreased conflicts and maintain larger territories when overlapping with kin, though not when overlapping with nonkin. More generally, it is possible that kinship extends the “dear enemy” effect in animal societies.     

DNA methyltransferase-3–dependent nonrandom template segregation in differentiating embryonic stem cells

Asymmetry of cell fate is one fundamental property of stem cells, in which one daughter cell self-renews, whereas the other differentiates. Evidence of nonrandom template segregation (NRTS) of chromosomes during asymmetric cell divisions in phylogenetically divergent organisms, such as plants, fungi, and mammals, has already been shown. However, before this current work, asymmetric inheritance of chromatids has never been demonstrated in differentiating embryonic stem cells (ESCs), and its molecular mechanism has remained unknown. Our results unambiguously demonstrate NRTS in asymmetrically dividing, differentiating human and mouse ESCs. Moreover, we show that NRTS is dependent on DNA methylation and on Dnmt3 (DNA methyltransferase-3), indicating a molecular mechanism that regulates this phenomenon. Furthermore, our data support the hypothesis that retention of chromatids with the “old” template DNA preserves the epigenetic memory of cell fate, whereas localization of “new” DNA strands and de novo DNA methyltransferase to the lineage-destined daughter cell facilitates epigenetic adaptation to a new cell fate.     

Association Mapping in Outbred Populations: Power and Efficiency When Genotyping Parents and Phenotyping Progeny

We develop expressions for the power to detect associations between parental genotypes and offspring phenotypes for quantitative traits. Three different “indirect” experimental designs are considered: full-sib, half-sib, and full-sib–half-sib families. We compare the power of these designs to detect genotype–phenotype associations relative to the common, “direct,” approach of genotyping and phenotyping the same individuals. When heritability is low, the indirect designs can outperform the direct method. However, the extra power comes at a cost due to an increased phenotyping effort. By developing expressions for optimal experimental designs given the cost of phenotyping relative to genotyping, we show how the extra costs associated with phenotyping a large number of individuals will influence experimental design decisions. Our results suggest that indirect association studies can be a powerful means of detecting allelic associations in outbred populations of species for which genotyping and phenotyping the same individuals is impractical and for life history and behavioral traits that are heavily influenced by environmental variance and therefore best measured on groups of individuals. Indirect association studies are likely to be favored only on purely economical grounds, however, when phenotyping is substantially less expensive than genotyping. A web-based application implementing our expressions has been developed to aid in the design of indirect association studies.