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With the desire to model population genetic processes under increasingly realistic scenarios, forward genetic simulations have become a critical part of the toolbox of modern evolutionary biology. The SLiM forward genetic simulation framework is one of the most powerful and widely used tools in this area. However, its foundation in the Wright-Fisher model has been found to pose an obstacle to implementing many types of models; it is difficult to adapt the Wright-Fisher model, with its many assumptions, to modeling ecologically realistic scenarios such as explicit space, overlapping generations, individual variation in reproduction, density-dependent population regulation, individual variation in dispersal or migration, local extinction and recolonization, mating between subpopulations, age structure, fitness-based survival and hard selection, emergent sex ratios, and so forth. In response to this need, we here introduce SLiM 3, which contains two key advancements aimed at abolishing these limitations. First, the new non-Wright-Fisher or "nonWF" model type provides a much more flexible foundation that allows the easy implementation of all of the above scenarios and many more. Second, SLiM 3 adds support for continuous space, including spatial interactions and spatial maps of environmental variables. We provide a conceptual overview of these new features, and present several example models to illustrate their use.
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http://dx.doi.org/10.1093/molbev/msy228 | DOI Listing |
EMBO Rep
September 2025
Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287, Darmstadt, Germany.
The flexibility of the spatio-temporal genome replication program during development and disease highlights the regulatory role of plastic epigenetic mechanisms over genetic determinants. Histone post-translational modifications are broadly implicated in replication timing control, yet the specific mechanisms through which individual histone marks influence replication dynamics, particularly in heterochromatin, remain unclear. Here, we demonstrate that H3K36me3 dynamically enriches at pericentromeric heterochromatin, composed of major satellite DNA repeats, prior to replication during mid S phase in mouse embryonic stem cells.
View Article and Find Full Text PDFJCI Insight
September 2025
Division of Metabolism, Endocrinology & Diabetes, and.
Intracellular trafficking of secretory and membrane proteins from the endoplasmic reticulum (ER) to the cell surface, via the secretory pathway, is crucial to the differentiated function of epithelial tissues. In the thyroid gland, a prerequisite for such trafficking is proper protein folding in the ER, assisted by an array of ER molecular chaperones. One of the most abundant of these chaperones, Glucose-Regulated-Protein-170 (GRP170, encoded by Hyou1), is a noncanonical hsp70-like family member.
View Article and Find Full Text PDFMedicine (Baltimore)
September 2025
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Although the potential causal associations between cell-derived signaling molecules and sleep disorder (SD) have been reported, contradictions remain. This study assessed the causal effects and the mediating role of 1400 metabolites among 91 cell-derived signaling molecules and SD from a genetic perspective by performing Mendelian randomization (MR) analyses. Genetic instruments derived from publicly available genome-wide association studies were employed in this study, including 49,880 SD cases and 358,194 controls.
View Article and Find Full Text PDFNew Phytol
September 2025
College of Biology, Hunan University, Changsha, 410082, China.
In legume root nodules, rhizobia invade host cells to form symbiosomes that drive atmospheric nitrogen fixation. Although the metabolic roles of infected cells (ICs) are well established, the contributions of adjacent uninfected cells (UCs) have remained largely unexplored. Here, through forward genetics methods, we identify DEBINO4, a phosphoenolpyruvate carboxylase (PEPC) uniquely expressed in UCs, as a pivotal regulator of carbon metabolism essential for sustaining symbiosome function and nitrogen assimilation.
View Article and Find Full Text PDFOpen Med (Wars)
August 2025
Department of Traditional Chinese Medicine, Shanghai Chongming District Hospital of Traditional Chinese and Western Medicine, Shanghai, 202153, China.
Background: Emerging evidence suggests that hemorrhoids are associated with cardiovascular disease (CVD). However, the causal associations between hemorrhoids and CVD remain elusive. This study aimed to investigate potential causal links between hemorrhoids and various heart conditions, including arrhythmia, heart failure, myocardial infarction, atrial fibrillation, and coronary artery disease.
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