Antagonistic selection between different fitness components (e.g., survival versus fertility) or different types of individuals in a population (e.g., females versus males) can potentially maintain genetic diversity and thereby account for the high levels of fitness variation observed in natural populations. However, the degree to which antagonistic selection can maintain genetic variation critically depends on the dominance relations between antagonistically selected alleles in diploid individuals. Conditions for stable polymorphism of antagonistically selected alleles are narrow, particularly when selection is weak, unless the alleles exhibit "dominance reversals"-in which each allele is partially or completely dominant in selective contexts in which it is favored and recessive in contexts in which it is harmful. Although theory predicts that dominance reversals should emerge under biologically plausible conditions, evidence for dominance reversals is sparse. In this primer, we review theoretical arguments and data supporting a role for dominance reversals in the maintenance of genetic variation. We then highlight an illuminating new study by Grieshop and Arnqvist, which reports a genome-wide signal of dominance reversals between male and female fitness in seed beetles.
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http://dx.doi.org/10.1371/journal.pbio.3000118 | DOI Listing |
Anal Chem
January 2025
Waters Corporation, 34 Maple St., Milford, Massachusetts 01757, United States.
Therapeutic drugs and multivalent vaccines based on the delivery of mRNA via lipid nanoparticle (LNP) technologies are expected to dominate the biopharmaceutical industry landscape in the coming years. Many of these innovative therapies include several nucleic acid components (e.g.
View Article and Find Full Text PDFStroke
January 2025
Neurology and Radiology, Massachusetts General Hospital, UNITED STATES.
Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease. This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations.
View Article and Find Full Text PDFNature
January 2025
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites. Such modifications have been proposed to trigger the selective removal of chemically marked proteins; however, identifying modifications that are sufficient to induce protein degradation has remained challenging.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Swansea Lab for Animal Movement, Biosciences, College of Science, Swansea University, Swansea, Wales SA2 8PP, United Kingdom.
Large herbivores are in decline in much of the world, including sub-Saharan Africa, and true apex carnivores like the lion () decline in parallel with their prey. As a consequence, competitively subordinate carnivores like the African wild dog () are simultaneously experiencing a costly reduction in resources and a beneficial reduction in dominant competitors. The net effect is not intuitively obvious, but wild dogs' density, survival, and reproduction are all low in areas that are strongly affected by prey depletion.
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