Empirical testing of hypotheses about the evolution of genomic imprinting in mammals

The close interaction between mother and offspring in mammals is thought to contribute to the evolution of genomic imprinting or parent-of-origin dependent gene expression. Empirical tests of theories about the evolution of imprinting have been scant for several reasons. Models make different assumptions about the traits affected by imprinted genes and the scenarios in which imprinting is predicted to have been selected for. Thus, competing hypotheses cannot readily be tested against each other. Further, it is far from clear how predictions about expression patterns of genes with specific phenotypic effects can be tested given current methodology of assaying gene expression levels, be it in the brain or in other tissues. We first set out a scenario for testing competing hypotheses and delineate the different assumptions and predictions of models. We then outline how predictions may be tested using mouse models such as intercrosses or recombinant inbred (RI) systems that can be phenotyped for traits relevant to imprinting theories. Further, we briefly discuss different molecular approaches that may be used in conjunction with experiments to ascertain expression patterns of imprinted genes and thus the testing of predictions

Этическая направленность критического мышления учителя

Объектом анализа в статье является этическая направленность критического мышления учителя. Оценочность и рефлексивность осмысляются как характеристики критического мышления. Обосновывается, что этические рационализации придают этическую направленность критическому мышлению педагога при решении им ситуаций с нравственным содержанием. Показывается, каким образом в процессе профессионального обучения может происходить формирование категориального аппарата этического мышления будущего учителя, придающего этическую направленность его критическому мышлени

Novel resilience in response to revitalisation after exposure to lethal salinity causes differential reproductive success in an extremely plastic organism

Phenotypic plasticity is central to an organism’s ability to adapt to variable environmental conditions. For aquatic organisms, exposure to elevated salt levels poses a challenge and organisms may fail to tolerate or survive much higher levels short-term. Here we demonstrate, for the first time, in a laboratory study of Daphnia magna that exposure to levels of salinity higher than those previously shown to lead to apparent death (paralysis) can be reversed following a transfer to optimal conditions. We established experimental populations from one clone of D. magna, each with five replicates, that were exposed to different short periods of three different lethal levels of salinity (12.27 PSU [45, 60, 90 and 120 min], 18.24 PSU [45, 60 and 90 min] and 24.22 PSU [45, 60 and 90 min]). In all populations, all individuals were paralysed at the end of their exposure, usually classified in the literature as dead. Subsequently, all individuals were transferred to optimal conditions. However, after the transfer, a proportion of the individuals not only came back from the verge of death (i.e. were revitalised), but also showed afterwards differential reproductive success over a period of 20 days, depending on the level and the length of exposure before revitalisation. Both exposure level and time had an overall negative effect on population size that differed across all treatments. Revitalisation occurred within an hour after the transfer to optimal conditions for 18.24 PSU but took 14–16 h for 12.27 PSU. There was no instantaneous revitalisation nor was there any revitalisation after 16 h no matter how long the paralysed Daphnia individuals were left in the optimal conditions. Our findings cast new light on resilience in cladocerans and suggest that abrupt environmental change can reveal novel plastic responses to extreme conditions

Social stability in semiferal ponies: networks show interannual stability alongside seasonal flexibility

Long-term relationships that underlie many stable mammalian groups often occur between philopatric kin. Although stable groups of nonrelatives appear to be less common, there is increasing evidence that social bonds between nonkin may confer sufficient intrinsic fitness benefits for these groups to persist. Here we evaluate whether social stability occurs in a bisexually dispersing species where social bonds have been shown to have reproductive benefits: the feral horse, Equus caballus. First, we quantified female social stability by applying a three-level framework to a 3-year data set of associations in semiferal ponies; this tested for stability at the individual, dyadic and subpopulation levels. Despite the relative weakness of these female bonds, we found significant social stability across all levels, as shown by stable association preferences, social networks and individual network positions. Second, we investigated how seasonality impacts on social bond strength and grouping patterns. We found seasonal fluctuations in female gregariousness, with a peak during the mating season. We therefore propose that significant social stability in female horses is coupled with a degree of flexibility that allows for effects of ecological fluctuations. Although social network analysis is widely used in behavioural ecological research, this is one of only a handful of studies to assess the temporal dynamics of networks over a significant timescale. Temporal stability in female relationships suggests that equid social structures are multifaceted: although bonds between stallions and mares are clearly strong, long-term relationships between mares underpin the social network structure. We suggest this framework could be used to assess social stability in other group-living species in order to improve our understanding of the nature of social bonds

Sex dependent imprinting effects on complex traits in mice

BACKGROUND: Genomic imprinting is an epigenetic source of variation in quantitative traits that results from monoallelic gene expression, where commonly either only the paternally- or the maternally-derived allele is expressed. Imprinting has been shown to affect a diversity of complex traits in a variety of species. For several such quantitative traits sex-dependent genetic effects have been discovered, but whether imprinting effects also show such sex-dependence has yet to be explored. Moreover, theoretical work on the evolution of sex-dependent genomic imprinting effects makes specific predictions about the phenotypic patterns of such effects, which, however, have not been assessed empirically to date. RESULTS: Using a genome-scan for loci affecting a set of complex growth and body composition traits from an intercross between two divergent mouse strains, we investigated possible sex-dependent imprinting effects. Our results demonstrate for the first time the existence of genomic imprinting effects that depend on sex and are not related to sex-chromosome effects. We detected a total of 13 loci on 11 chromosomes that showed significant differences between the sexes in imprinting effects. Most loci showed imprinting effects in only one sex, with eight imprinted effects found in males and six in females. One locus showed sex-dependent imprinting effects in both sexes for different traits. The absence of an imprinting effect in one sex was not necessarily indicative of the overall inactivity of the locus in that sex, as for several loci a significant additive or dominance effect was detected. Moreover, three loci exhibited significant additive effects in both sexes but their imprinting effect was restricted to one sex. CONCLUSION: Our results clearly show that imprinting effects can be sex-dependent and also suggest that new candidate imprinted loci can be detected when taking account of sex-specific imprinting effects. However, predictions made about the evolution of sex-dependent imprinting effects and associated phenotypic patterns cannot be unequivocally supported at present and further research into the selection pressures applied to the strains of mice used in our study is required

Maternal Immune Activation Induces Adolescent Cognitive Deficits Preceded by Developmental Perturbations in Cortical Reelin Signalling.

Exposure to maternal immune activation (MIA) in utero significantly elevates the risk of developing schizophrenia and other neurodevelopmental disorders. To understand the biological mechanisms underlying the link between MIA and increased risk, preclinical animal models have focussed on specific signalling pathways in the brain that mediate symptoms associated with neurodevelopmental disorders such as cognitive dysfunction. Reelin signalling in multiple brain regions is involved in neuronal migration, synaptic plasticity and long-term potentiation, and has been implicated in cognitive deficits. However, how regulation of Reelin expression is affected by MIA across cortical development and associated cognitive functions remains largely unclear. Using a MIA rat model, here we demonstrate cognitive deficits in adolescent object-location memory in MIA offspring and reductions in Reln expression prenatally and in the adult prefrontal cortex. Further, developmental disturbances in gene/protein expression and DNA methylation of downstream signalling components occurred subsequent to MIA-induced Reelin dysregulation and prior to cognitive deficits. We propose that MIA-induced dysregulation of Reelin signalling contributes to the emergence of prefrontal cortex-mediated cognitive deficits through altered NMDA receptor function, resulting in inefficient long-term potentiation. Our data suggest a developmental window during which attenuation of Reelin signalling may provide a possible therapeutic target

A Maternal–Offspring Coadaptation Theory for the Evolution of Genomic Imprinting

Imprinted genes are expressed either from the maternally or paternally inherited copy only, and they play a key role in regulating complex biological processes, including offspring development and mother–offspring interactions. There are several competing theories attempting to explain the evolutionary origin of this monoallelic pattern of gene expression, but a prevailing view has emerged that holds that genomic imprinting is a consequence of conflict between maternal and paternal gene copies over maternal investment. However, many imprinting patterns and the apparent overabundance of maternally expressed genes remain unexplained and may be incompatible with current theory. Here we demonstrate that sole expression of maternal gene copies is favored by natural selection because it increases the adaptive integration of offspring and maternal genomes, leading to higher offspring fitness. This novel coadaptation theory for the evolution of genomic imprinting is consistent with results of recent studies on epigenetic effects, and it provides a testable hypothesis for the origin of previously unexplained major imprinting patterns across different taxa. In conjunction with existing hypotheses, our results suggest that imprinting may have evolved due to different selective pressures at different loci

Maternal behaviours and adult offspring behavioural deficits are predicted by maternal TNFα concentration in a rat model of neurodevelopmental disorders

Exposure to inflammatory stressors during fetal development is a major risk factor for neurodevelopmental disorders (NDDs) in adult offspring. Maternal immune activation (MIA), induced by infection, causes an acute increase in pro-inflammatory cytokines which can increase the risk for NDDs directly by inducing placental and fetal brain inflammation, or indirectly through affecting maternal care behaviours thereby affecting postnatal brain development. Which of these two potential mechanisms dominates in increasing offspring risk for NDDs remains unclear. Here, we show that acute systemic maternal inflammation induced by the viral mimetic polyinosinic:polycytidylic acid (poly I:C) on gestational day 15 of rat pregnancy affects offspring and maternal behaviour, offspring cognition, and expression of NDD-relevant genes in the offspring brain. Dams exposed to poly I:C elicited an acute increase in the pro-inflammatory cytokine tumour necrosis factor (TNF; referred to here as TNFα), which predicted disruption of key maternal care behaviours. Offspring of poly I:C-treated dams showed early behavioural and adult cognitive deficits correlated to the maternal TNFα response, but, importantly, not with altered maternal care. We also found interacting effects of sex and treatment on GABAergic gene expression and DNA methylation in these offspring in a brain region-specific manner, including increased parvalbumin expression in the female adolescent frontal cortex. We conclude that the MIA-induced elevation of TNFα in the maternal compartment affects fetal neurodevelopment leading to altered offspring behaviour and cognition. Our results suggest that a focus on prenatal pathways affecting fetal neurodevelopment would provide greater insights into the mechanisms underpinning the TNFα-mediated genesis of altered offspring behaviour and cognition following maternal inflammation

Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice

Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene-targeting techniques have allowed for the identification of imprinted loci, very little is known about the contribution of imprinting to quantitative variation in complex traits. Most studies, furthermore, assume a simple pattern of imprinting, resulting in either paternal or maternal gene expression; yet, more complex patterns of effects also exist. As a result, the distribution and number of different imprinting patterns across the genome remain largely unexplored. We address these unresolved issues using a genome-wide scan for imprinted quantitative trait loci (iQTL) affecting body weight and growth in mice using a novel three-generation design. We identified ten iQTL that display much more complex and diverse effect patterns than previously assumed, including four loci with effects similar to the callipyge mutation found in sheep. Three loci display a new phenotypic pattern that we refer to as bipolar dominance, where the two heterozygotes are different from each other while the two homozygotes are identical to each other. Our study furthermore detected a paternally expressed iQTL on Chromosome 7 in a region containing a known imprinting cluster with many paternally expressed genes. Surprisingly, the effects of the iQTL were mostly restricted to traits expressed after weaning. Our results imply that the quantitative effects of an imprinted allele at a locus depend both on its parent of origin and the allele it is paired with. Our findings also show that the imprinting pattern of a locus can be variable over ontogenetic time and, in contrast to current views, may often be stronger at later stages in life

Social Selection and Indirect Genetic Effects in Structured populations

Social selection and indirect genetic effects (IGEs) are established concepts in both behavioural ecology and evolutionary genetics. While IGEs describe effects of an individual’s genotype on phenotypes of social partners (and may thus affect their fitness indirectly), the concept of social selection assumes that a given phenotype in one individual affects the fitness of other individuals directly. Although different frameworks, both have been used to investigate the evolution of social traits, such as cooperative behaviour. Despite their similarities (both concepts consider interactions among individuals), they differ in the type of interaction. It remains unclear whether the two concepts make the same predictions about evolutionary trajectories or not. To address this question, we investigate four possible scenarios of social interactions and compare the effects of IGEs and social selection for trait evolution in a multi-trait multi-member model. We show that the two mechanisms can yield similar evolutionary outcomes and that both can create selection pressure at the group level. However, the effect of IGEs can be stronger due to the possibility of feedback loops. Finally, we demonstrate that IGEs, but not social selection gradients, may lead to differences in the direction of evolutionary response between genotypes and phenotypes