Biology subjects

de Vries, C.

Publications and source records attributed to de Vries, C..

6 recordsLinked to original sources

bioRxiv2025

Modulation of Nur77-DNA Interactions by the Glucocorticoid Receptor

Nuclear receptors (NRs) comprise a superfamily of (ligand-)regulated transcription factors that are pivotal in orchestrating gene networks essential for development, metabolism, and cellular homeostasis. Their activity is critical for normal physiology, and consequently, dysregulation of NR signaling is implicated in a wide array of human diseases. Within this superfamily, the orphan nuclear receptor Nur77 and the glucocorticoid receptor (GR) are key regulators that exhibit significant crosstalk, primarily antagonistic, which is crucial for modulating inflammatory and stress responses. Despite the recognized importance of their interplay, the precise molecular mechanisms by which GR modulates Nur77s engagement with DNA remain incompletely defined. This study elucidates the direct impact of GR and its ligand, dexamethasone (Dex), on the DNA binding dynamics of Nur77. Single-molecule DNA tightrope assays revealed that Nur77 employs a three-dimensional diffusion-based search mechanism on non-specific DNA, characterized by transient interactions with two distinct dissociation kinetic profiles. GR significantly stabilizes Nur77-DNA interactions, evidenced by a shift towards longer residence times, primarily achieved by slowing the dissociation of the more transiently interacting Nur77 population. Conversely, single-molecule analysis and biochemical assays demonstrated that Dex alone markedly reduces Nur77s overall DNA binding affinity kinetics and frequency in a sequence-dependent manner, to such an extent that accurate quantification was unfeasible. These findings delineate distinct modulatory effects of the GR protein and its ligand on Nur77-DNA interactions, providing crucial biophysical insights into their complex regulatory interplay and revealing a direct, GR-independent impact of dexamethasone on Nur77s DNA engagement. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/685035v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@1207cdorg.highwire.dtl.DTLVardef@1be29eborg.highwire.dtl.DTLVardef@1b23eaaorg.highwire.dtl.DTLVardef@13030b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Asymmetric life-history trade-offs shape sex-biased longevity patterns

Sex differences in ageing and lifespan are widespread across taxa, yet their evolutionary causes remain debated. A leading hypothesis suggests these differences are adaptive and driven by sex-specific life-history trade-offs, but formal theoretical support is lacking. To address this, we developed a mathematical model to investigate how such trade-offs shape lifespan evolution in a monogamous mating system. In the model, individuals evolve to optimise a trade-off between reproduction and survival - mediated by mating opportunities in males and offspring production in females. By systematically varying trade-off strengths, we show that either sex can evolve greater longevity, but male-biased longevity evolves under a broader set of conditions - consistent with patterns in monogamous species. This asymmetry arises because female longevity is more constrained: the trade-off between offspring production and survival directly affects the fertility of both sexes. In contrast, the male trade-off for mating opportunities has a weaker indirect effect on female fertility, allowing selection to more readily favour longer male lifespans. We also show that extrinsic density-dependent mortality can disproportionately affect the intrinsically longer-living sex, and obscure the magnitude of this evolved difference. Together, our results provide new theoretical insights into the adaptive bases of sex-biased longevity and highlight the importance of life-history trade-offs in shaping lifespan evolution.

evolutionary biology↗

bioRxiv2025

The formal demography of kinship. VII. Lifetime kin overlap within and across generations

BackgroundInteractions among kin have important consequences, including resource transfers, alloparenting, health care, and economic support. Some interactions require that the lives of the interacting relatives overlap. The overlap over a lifetime (lifetime kin overlap, LKO) depends on mortality (longer lives give more opportunity for overlap) and fertility (higher fertility produces more kin with which to overlap). Here we provide a general solution to the problem of calculating lifetime kin overlap. ObjectivesTo develop a demographic model for the mean and variance of the lifetime overlap of any types of kin over the life of a focal individual. MethodsThe matrix kinship model is used to provide the age distribution of kin as an age-specific property of Focal. The mean and variance of lifetime overlap with kin of any type are then calculated using Markov chains with rewards. ResultsWe obtain the statistics of LKO with numbers of kin, with selected age classes of kin, and with at least one kin, in both prospective and retrospective directions, for each sex separately and with sexes combined. Simultaneous overlap with two or more types of kin (e.g., parents and children) describes sandwich generations. We provide an example comparing Japan under 1947 rates (low survival, high fertility) and 2019 rates (high survival, low fertility). ContributionIt is now possible to compute the mean and variance of the projected LKO with any type of kin, in one-sex or two-sex models based on age or combinations of age and stage.

ecology↗

bioRxiv2022

A note on discretising Keyfitz entropy

Keyfitz entropy is a widely used metric to quantify the shape of survivorship of populations, from plants, to animals, and microbes. Keyfitz entropy values < 1 correspond to life histories with an increasing mortality rate with age (i.e., actuarial senescence), whereas values > 1 correspond to species with a decreasing mortality rate with age (negative senescence), and a Keyfitz entropy of exactly 1 corresponds to a constant mortality rate with age. Keyfitz entropy was originally defined using a continuous-time model, and has since been discretised to facilitate its calculation from discrete-time demographic data. In this short note, we show that the previously used discretisation of the continuous-time metric does not preserve the relationship with increasing, decreasing, or constant mortality rates. To resolve this discrepancy, we propose a new discrete-time formula for Keyfitz entropy for age-classified life histories. We show that this new method of discretisation preserves the relationship with increasing, decreasing, or constant mortality rates. We analyse the relationship between the original and the new discretisation, and we find that the existing metric tends to underestimate Keyfitz entropy for both short-lived species and long-lived species, thereby introducing a consistent bias. To conclude, to avoid biases when classifying life histories as (non-)senescent, we suggest researchers use either the new metric proposed here, or one of the many previously suggested survivorship shape metrics applicable to discrete-time demographic data such as Gini coefficient or Hayleys median.

ecology↗

bioRxiv2022

Positive fitness effects help explain the broad range of Wolbachia prevalences in natural populations

The bacterial endosymbiont Wolbachia is best known for its ability to modify its hosts reproduction by inducing cytoplasmic incompatibility (CI) to facilitate its own spread. Classical models predict either near-fixation of costly Wolbachia once the symbiont has overcome a threshold frequency (invasion barrier), or Wolbachia extinction if the barrier is not overcome. However, natural populations do not all follow this pattern: Wolbachia can also be found at low frequencies (below one half) that appear stable over time. Wolbachia is known to have pleiotropic fitness effects (beyond CI) on its hosts. Existing models typically focus on the possibility that these are negative. Here we consider the possibility that the symbiont provides direct benefits to infected females (e.g. resistance to pathogens) in addition to CI. We discuss an underappreciated feature of Wolbachia dynamics: that CI with additional fitness benefits can produce low-frequency (< 1/2) stable equilibria. Additionally, without a direct positive fitness effect, any stable equilibrium close to one half will be sensitive to perturbations, which make such equilibria unlikely to sustain in nature. The results hold for both diplodiploid and different haplodiploid versions of CI. We suggest that insect populations showing low-frequency Wolbachia infection might host CI-inducing symbiotic strains providing additional (hidden or known) benefits to their hosts, especially when classical explanations (ongoing invasion, source-sink dynamics) have been ruled out.

ecology↗

bioRxiv2022

The demographic costs of sexually antagonistic selection in partially selfing populations

Classic population genetics theory has been fundamental to understanding the evolution of sex-differences and the maintenance of sexually antagonistic (SA) genetic variation, but these models have rarely considered the demographic consequences of intralocus sexual antagonism. In this paper we develop a stage-structured mendelian matrix model and jointly analyze the evolutionary and demographic consequences of SA selection in obligately outcrossing (i.e., dioecious/gonochorous) and partially selfing hermaphrodite populations. We focus on identifying parameter conditions under which SA polymorphism is maintained and the population growth rate remains positive. Additionally, we analyze the effects of inbreeding depression manifesting at different life-history stages and give an illustrative example of the potential for SA polymorphism in real populations using empirically estimated demographic rates for the hermaphroditic flowering plant Mimulus guttatus. Our results show that when population intrinsic growth rates approach one, extinction occurs across large swathes of parameter space favoring SA polymorphism or the fixation of male-beneficial alleles, and that inbreeding depression is a significant problem for maintaining SA polymorphism in partially selfing populations. Despite these demographic challenges, our example with M. guttatus appears to show that demographic rates observed in some real populations are capable of sustaining large regions of viable SA polymorphic space.

evolutionary biology↗