Biology subjects

Berger, D.

Publications and source records attributed to Berger, D..

29 records · Page 2Linked to original sources

bioRxiv2021

The mating system affects the temperature sensitivity of male and female fertility

O_LITo mitigate effects of climate change it is important to understand species responses to increasing temperatures. This has often been done by studying survival or activity at temperature extremes. Before such extremes are reached, however, effects on fertility may already be apparent. C_LIO_LISex differences in the thermal sensitivity of fertility (TSF) could impact species persistence under climate warming because female fertility is typically more limiting to population growth than male fertility. However, little is known about sex differences in TSF. C_LIO_LIHere we first demonstrate that the mating system can strongly influence TSF using the seed beetle Callosobruchus maculatus. We exposed populations carrying artificially induced mutations to two generations of short-term experimental evolution under alternative mating systems, manipulating the opportunity for natural and sexual selection on the mutations. We then measured TSF in males and females subjected to juvenile or adult heat stress. C_LIO_LIPopulations kept under natural and sexual selection had higher fitness, but similar TSF, compared to control populations kept under relaxed selection. However, females had higher TSF than males, and strikingly, this sex difference had increased over only two generations in populations evolving under sexual selection. C_LIO_LIWe hypothesized that an increase in male-induced harm to females during mating had played a central role in driving this evolved sex difference, and indeed, remating under conditions limiting male harassment of females reduced both male and female TSF. Moreover, we show that manipulation of mating system parameters in C. maculatus generates intraspecific variation in the sex difference in TSF equal to that found among a diverse set of studies on insects. C_LIO_LIOur study provides a causal link between the mating system and TSF. Sexual conflict, (re)mating rates, and genetic responses to sexual selection differ among ecological settings, mating systems and species. Our study therefore also provides mechanistic understanding for the variability in previously reported TSFs which can inform future experimental assays and predictions of species responses to climate warming. C_LI

ecology↗

bioRxiv2021

macroH2A2 shapes chromatin accessibility at enhancer elements in glioblastoma to modulate a targetable self-renewal epigenetic network

Self-renewal is a crucial property of glioblastoma cells and is enabled by the choreographed function of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could represent an important step toward developing new and effective treatments for this universally lethal cancer. Here we uncover a targetable epigenetic axis of self-renewal mediated by the histone variant macroH2A2. Using patient-derived in vitro and in vivo models, we show that macroH2A2 has a direct role in shaping chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. Pharmaceutical inhibition of the chromatin remodeler Menin increased macroH2A2 levels and repressed self- renewal. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest new treatment approaches for glioblastoma patients. SIGNIFICANCEGlioblastoma is an incurable brain cancer. Malignant self-renewing cells have been shown to drive tumor growth, to be refractory to current treatment approaches and to seed relapses, which ultimately prove lethal. Identifying new and targetable mechanisms associated with self-renewal could be a fundamental first step in designing effective therapies that slow or prevent glioblastoma relapses. Using patient-derived models of glioblastoma, we deployed epigenomic approaches and functional assays to define the role of the histone variant macroH2A2 in repressing self-renewal. We identified compounds that increase macroH2A2 levels and repress self-renewal, including a Menin inhibitor. As Menin inhibitors are being tested in clinical trials, these compounds could be used in new therapeutic paradigms to target self-renewing cell populations in glioblastoma.

cancer biology↗

bioRxiv2020

Sexual conflict drives micro- and macroevolution of sexual dimorphism in immunity

BackgroundSexual selection can have major effects on mating rates and sex-specific costs of mating and may thereby influence sex-differences in immunity as well as associated host-pathogen dynamics. Yet, experimental evidence linking the mating system to evolved sexual dimorphism in immunity are scarce and the direct effects of mating rate on immunity are not well established. Here, we use transcriptomic analyses, experimental evolution and phylogenetic comparative methods to study the association between the mating system and sexual dimorphism in immunity in seed beetles, where mating causes internal injuries in females. ResultsWe demonstrate that female phenoloxidase (PO) activity, involved in wound healing and defence against parasitic infections, is elevated relative to males. This difference is accompanied by concomitant sex-differences in the expression of genes in the pro-phenoloxidase activating cascade. We document substantial phenotypic plasticity in female PO activity in response to mating and show that experimental evolution under enforced monogamy (resulting in low remating rates and sexual conflict relative to natural polygamy) rapidly decreases female (but not male) PO activity. Moreover, monogamous females have evolved increased tolerance to bacterial infection unrelated to mating, implying that female responses to costly mating may trade off with other aspects of immune defence, an hypothesis which broadly accords with the documented sex differences in gene expression. Finally, female (but not male) PO activity shows correlated evolution with the perceived harmfulness of male genitalia across 12 species of seed beetles, suggesting that sexual conflict has a significant influence on sexual dimorphisms in immunity in this group of insects. ConclusionsOur study provides insights into the links between sexual conflict and sexual dimorphism in immunity at the molecular and phenotypic level and suggests that selection pressures moulded by mating interactions can lead to a sex-specific mosaic of immune responses with important implications for host-pathogen dynamics in sexually reproducing organisms.

evolutionary biology↗

bioRxiv2020

Selection in males purges the standing genetic load on female fitness

Theory predicts that the ability of selection and recombination to purge mutation load is enhanced if selection against deleterious genetic variants operates more strongly in males than females. However, direct empirical support for this tenet is limited, in part because traditional quantitative genetic approaches allow dominance and intermediate-frequency polymorphisms to obscure the effects of the many rare and partially recessive deleterious alleles that make up the main part of a populations mutation load. Here, we exposed the partially recessive genetic load of a population of Callosobruchus maculatus seed beetles via successive generations of inbreeding, and quantified its effects by measuring heterosis - the increase in fitness experienced when masking the effects of deleterious alleles by heterozygosity - in a fully factorial sex-specific diallel cross among 16 inbred strains. Competitive lifetime reproductive success (i.e. fitness) was measured in male and female outcrossed F1s as well as inbred parental selfs, and we estimated the 4x4 male-female inbred-outbred genetic covariance matrix for fitness using Bayesian Markov chain Monte Carlo simulations of a custom-made general linear mixed effects model. We found that heterosis estimated independently in males and females was highly genetically correlated among strains, and that heterosis was strongly negatively genetically correlated to outbred male, but not female, fitness. This suggests that genetic variation for fitness in males, but not in females, reflects the amount of (partially) recessive deleterious alleles segregating at mutation-selection balance in this population. The populations mutation load therefore has greater potential to be purged via selection in males. These findings contribute to our understanding of the prevalence of sexual reproduction in nature and the maintenance of genetic variation in fitness-related traits. Impact statementWhy do the large majority of eukaryotic species reproduce sexually if it means that females must spend half of their reproductive effort producing males, while males contribute few or no resources to offspring production themselves? In principle, a lineage of a mutant asexual female that simply clones herself into daughters would grow at twice the rate of her sexual competitors (all else equal). What prevents this from being the predominant mode of reproduction throughout eukaryotes? One hypothesis regards the role of males in facilitating the purging of deleterious mutations from the populations genome since very strong selection in males, unlike selection in females, can occur in many species without reductions in population offspring numbers. Due to the inherent difficulties of isolating this source of standing genetic variation for fitness, empirical evidence for this theory is mixed and limited to indirect evidence from manipulative experiments and experimental evolution studies. Here we demonstrate that recessive deleterious alleles in a population of the seed beetle, Callosobruchus maculatus, are selected against strongly in males but not females. Using a fully factorial diallel cross among 16 inbred strains, we measured the degree to which fitness in the outbred offspring of those crosses improved relative to their inbred parents. This measure is known as heterosis and offers an estimate of the relative amount of partially recessive deleterious alleles carried by a genetic strain. We then analyzed the relationship between the strains heterosis values and their additive genetic breeding values for fitness measured in males and females, revealing the extent to which segregating (partially recessive) deleterious alleles are selected against in males and females. We found that a strains heterosis value was strongly genetically correlated with its additive genetic breeding value for male fitness, but not female fitness. This suggests that mutations with deleterious effects on population growth rate due to their effects on females can be selected against (i.e. purged) more efficiently via their male siblings. This process would offer a benefit to sexual reproduction that may partly compensate for its costs, and therefore yields insight to the prevalence of sex in nature.

evolutionary biology↗

bioRxiv2019

Evaluation of DNA extraction methods on individual helminth egg and larval stages for whole genome sequencing

Whole genome sequencing is being rapidly applied to the study of helminth genomes, including de novo genome assembly, population genetics, and diagnostic applications. Although late-stage juvenile and adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in the live host; immature life stages found in the environment for which samples can be collected non-invasively offer a potential alternative, however, these samples are typically yield very low quantities of DNA, can be environmentally resistant, and are susceptible to contamination, often from bacterial or host DNA. Here, we have tested five low-input DNA extraction protocols together with a low-input sequencing library protocol to assess the feasibility of whole genome sequencing of individual immature helminth samples. These approaches do not use whole genome amplification, a common but costly approach to increase the yield of low input samples. We first tested individual parasites from two species spotted onto FTA cards - egg and L1 stages of Haemonchus contortus and miracidia of Schistosoma mansoni - before further testing on an additional six species - Ancylostoma caninum, Ascaridia dissimilis, Dirofilaria immitis, Dracunculus medinensis, Strongyloides stercoralis, and Trichuris muris - with an optimal protocol. Whole genome sequencing followed by analyses to determine the proportion of on- and off-target mapping revealed successful sample preparations for six of the eight species tested with variation between species, and within species but between life stages, described. These results demonstrate the feasibility of whole genome sequencing of individual parasites, and highlight a new avenue towards generating sensitive, specific, and information-rich data for the diagnosis and surveillance of helminths.

genomics↗

bioRxiv2019

Sexual selection and the evolution of male and female cognition: a test using experimental evolution in seed beetles

\"The mating mind hypothesis\", originally aimed at explaining human cognition, holds that the socio-sexual environment shapes cognitive abilities among animals. Similarly, general sexual selection theory predicts that mate competition should benefit individuals carrying \"good genes\" with beneficial pleiotropic effects on general cognitive ability. However, few experimental studies have evaluated these related hypotheses due to difficulties of performing direct tests in most taxa. Here we harnessed the empirical potential of the seed beetle study system to investigate the role of sexual selection and mating system in the evolution of cognition. We evolved replicate lines of beetle under enforced monogamy (eliminating sexual selection) or polygamy for 35 generations and then challenged them to locate and discriminate among mating partners (male assays) or host seeds (female assays). To assess learning, the same beetles performed the task in three consecutive rounds. All lines learned the task, improving both within and between trails. Moreover, polygamous males outperformed monogamous males. However, there were no differences in the rate of learning between males of the two regimes, and polygamous females showed no improvement in host search, and even signs of reduced learning. Hence, while sexual selection was a potent factor that increased cognitive performance in mate search, it did not lead to the general increase in cognitive abilities expected under the \"mating mind\" hypothesis or general \"good genes\" theory. Our results highlight sexually antagonistic (balancing) selection as a potential force maintaining genetic variation in cognitive traits.

animal behavior and cognition↗

bioRxiv2018

Sexual selection, environmental robustness and evolutionary demography of maladapted populations: a test using experimental evolution in seed beetles.

Whether sexual selection impedes or aids adaptation has become a pressing question in times of rapid environmental change and parallels the debate about how the evolution of individual traits impacts on population dynamics and viability. The net effect of sexual selection on population viability results from a balance between genetic benefits of \"good genes\" effects and costs of sexual conflict. Depending on how these facets of sexual selection are affected under environmental change, extinction of maladapted populations could either be avoided or accelerated. Here, we evolved seed beetles under three alternative mating regimes (polygamy, monogamy and male-limited selection) to disentangle the contributions of sexual selection, fecundity selection and male-female coevolution to individual reproductive success and population fitness. We compared these contributions between the ancestral environment and two new stressful environments (temperature and host plant shift). Evolution under polygamy resulted in the highest individual reproductive success in competitive context for both sexes. Moreover, females evolving only via sexual selection on their male siblings in the male-limited regime had similar reproductive success and higher fertility than females evolving under monogamy, suggesting that sexual selection on males had positive effects on female fitness components. Interestingly, male-limited sexual selection resulted in males that were robust to stress, compared to males from the two evolution regimes applying fecundity selection. We quantified the population-level consequences of this sex-specific adaptation and found evidence that costs of socio-sexual interactions were higher in male-limited lines compared to polygamous lines, and that this difference was particularly pronounced at elevated temperature to which males from the male-limited regime were more robust compared to their conspecific females. These results illustrate the tension between individual-level adaptation and population-level viability in sexually reproducing species and suggest that sex-specific selection can cause differences in environmental robustness that may impact population demography under environmental change.

evolutionary biology↗

bioRxiv2018

Effects of host species and environmental factors on the prevalence of Batrachochytrium dendrobatidis in northern Europe

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is a major threat to amphibian populations. Here we asked if the prevalence of Bd differs between amphibian species and whether it is related to local environmental factors in breeding habitats as well as landscape variables measured at three scales (500, 2000 and 5000 m radius) in southernmost Sweden. We sampled 947 anurans from six species in 31 ponds. Canopy cover, pond perimeter, pH and temperature were treated as local scale pond characteristics. Number of surrounding ponds, area of arable land, area of mature forest and number of resident people were treated as landscape variables. Bufo bufo and Rana temporaria had a prevalence of 0.5-1.0% which differed strongly from the other four species (Bombina bombina, Bufotes variabilis, Epidalea calamita, Rana arvalis) showing 13-64% prevalence. Bd prevalence in these four species was higher in ponds with higher pH, surrounded by a landscape with less mature forest and few wetlands. Our results show that the infection dynamics of Bd are complex and depend on local pond characteristics, host community composition and the spatial scale under investigation. Information on environmental factors associated with Bd and species differences in susceptibility may mitigate further spread of the disease through public information and guide conservational action plans, especially for the most threatened species.

ecology↗

bioRxiv2018

The efficacy of sexual selection under environmental change

Sexual selection can promote adaptation if sexually selected traits are reliable indicators of genetic quality. Moreover, stronger sexual selection in males, as often reported in empirical studies, may help purge deleterious alleles at a low cost to population productivity. However, to what extent this remains true when a changing environment affects sexual selection dynamics has been debated. Here, we show that even if sexually selected traits remain honest signals of male quality in new environments, the efficacy of sexual selection will often be reduced under stress. We model the strength of sex-specific selection under different levels of environmental stress in a population in which males compete with each other for fertilization success and in which females experience fecundity selection. We observe that the strength of sexual selection is reduced relative to fecundity selection, resulting in a lowered potential for selection on males to aid adaptation under environmental change.

evolutionary biology↗

bioRxiv2018

A Universal Temperature-Dependence of Mutational Fitness Effects

Adaptation in new environments depends on the amount and type of genetic variation available for evolution, and the efficacy by which natural selection discriminates among this variation to favour the survival of the fittest. However, whether some environments systematically reveal more genetic variation in fitness, or impose stronger selection pressures than others, is typically not known. Here, we apply enzyme kinetic theory to show that rising global temperatures are predicted to intensify natural selection systematically throughout the genome by increasing the effects of DNA sequence variation on protein stability. We tested this prediction by i) estimating temperature-dependent fitness effects of induced random mutations in seed beetles adapted to ancestral or warm temperature, and ii) calculating 100 paired selection estimates on mutations in benign versus stressful environments from a diverse set of unicellular and multicellular organisms. Environmental stress per se did not increase the mean strength of selection on de novo mutation, suggesting that the cost of adaptation does not generally increase in new environments to which the organism is maladapted. However, elevated temperature increased the mean strength of selection on genome-wide polymorphism, signified by increases in both mutation load and mutational variance at elevated temperature. The theoretical predictions and empirical data suggest that this increase may correspond to a doubling of genome-wide selection for a predicted 2-4{degrees}C climate warming scenario in ectothermic organism living at temperatures close to their thermal optimum. These results have important implications for global patterns of genetic diversity and the rate and repeatability of evolution under climate change. Impact StatementNatural environments are constantly changing so organisms must also change to persist. Whether they can do so ultimately depends upon the reservoir of raw genetic material available for evolution, and the efficacy by which natural selection discriminates among this variation to favour the survival of the fittest. Here, the biochemical properties of molecules and proteins that underpin the link between genotype and phenotype can exert a major influence over how the physical environment affects the expression of phenotypes and the fitness consequences of DNA sequence polymorphism. Yet, the constraints set by these molecular features are often neglected within eco-evolutionary theory trying to predict evolution in new environments. Here we combine predictions from existing biophysical models of protein folding and enzyme kinetics with experimental data from ectothermic organisms across the tree of life, to show that rising global temperatures are predicted to increase the mean strength of selection on DNA sequence variation in cold-blooded organisms. We also show that environmental stress per se generally does not increase the mean strength of selection on new mutations, suggesting that genome-wide natural selection is not stronger in new environments to which an organism is maladapted. Theoretical predictions and data suggest that an expected climate warming scenario of a 2-4{degrees}C temperature raise within the forthcoming century will result in roughly a doubling of genome-wide selection for organisms living close to their thermal optima. However, our results also point to substantial variability in the temperature-dependence of selection on different proteins within and between organisms, suggesting scope for compensatory adaptation to shape this relationship. These results bear witness to and extend the universal temperature dependence of biological rates and have important implications for global patterns of genetic diversity and the rate and repeatability of genome evolution under environmental change.

evolutionary biology↗

bioRxiv2017

Improving the annotation of the Heterorhabditis bacteriophora genome

Genome assembly and annotation remains an exacting task. As the tools available for these tasks improve, it is useful to return to data produced with earlier instances to assess their credibility and correctness. The entomopathogenic nematode Heterorhabditis bacteriophora is widely used to control insect pests in horticulture. The genome sequence for this species was reported to encode an unusually high proportion of unique proteins and a paucity of secreted proteins compared to other related nematodes. We revisited the H. bacteriophora genome assembly and gene predictions to ask whether these unusual characteristics were biological or methodological in origin. We mapped an independent resequencing dataset to the genome and used the blobtools pipeline to identify potential contaminants. While present (0.2% of the genome span, 0.4% of predicted proteins), assembly contamination was not significant. Re-prediction of the gene set using BRAKER1 and published transcriptome data generated a predicted proteome that was very different from the published one. The new gene set had a much reduced complement of unique proteins, better completeness values that were in line with other related species genomes, and an increased number of proteins predicted to be secreted. It is thus likely that methodological issues drove the apparent uniqueness of the initial H. bacteriophora genome annotation and that similar contamination and misannotation issues affect other published genome assemblies.

bioinformatics↗