Biology subjects

Gaffney, K.

Publications and source records attributed to Gaffney, K..

3 recordsLinked to original sources

bioRxiv2026

Color polymorphism in the saddleback clownfish, Amphiprion polymnus: species or complex?

Color polymorphism can facilitate local adaptation, maintain intraspecific diversity, or reflect early stages of speciation. Clownfishes (Amphiprion spp.) typically display a simple black, orange, and white pattern, but the saddleback clownfish (Amphiprion polymnus) shows striking variation in melanism and the number of vertical bars, which are thought to play a role in species recognition. In 2024, a revision on iNaturalist split A. polymnus into multiple species based solely on color pattern and geographic range. This raises the question of whether these morphs represent true species or intraspecific polymorphism, which we tested using genomic and image-based data. We sampled 97 individuals from seven populations across the species range and quantified color patterns from standardized photographs. Phenotypic and genomic analyses reveal a complex pattern of divergence. Image analysis identified three distinct phenotypic clusters, with A. polymnus, A. annamensis, and A. laticlavius each showing consistent differences in saddle shape and vertical bar extent. ADMIXTURE resolved three distinct genetic groups corresponding to the morphs. Pairwise FST (0.54-0.71) and dxy indicate extremely high differentiation between A. polymnus and A. annamensis, consistent with species-level divergence, whereas A. laticlavius shows much lower differentiation from A. polymnus (FST 0.09-0.18) and higher differentiation from A. annamensis (FST 0.64-0.66). Overall, phenotypic and genomic data show structured variation, but the status of A. laticlavius remains ambiguous. Our study reveals clear and structured divergence across the full range, yet the taxonomic interpretation of this variation remains inherently challenging. The key question remains: do these patterns reflect a single polymorphic species or a complex of closely related species?

ecology↗

bioRxiv2026

Activation of the protective arm of renin-angiotensin system enhances mitochondrial turnover improving respiration and decreasing integrated stress response in a human Complex III deficiency model.

Primary mitochondrial diseases are clinically and genetically heterogeneous disorders, commonly caused by defects in the oxidative phosphorylation system. This heterogeneity presents major challenges for therapeutic development; however, a shared hallmark across these diseases is the accumulation of dysfunctional mitochondria. Enhancing mitochondrial turnover, by activating the selective degradation of dysfunctional mitochondria via mitophagy, concurrently with the activation of mitochondrial biogenesis, could represent a shared therapeutic strategy for mitochondrial diseases. Here, we describe a novel mitophagy inducer, CAP-1902. CAP-1902 is a new agonist of the MAS G-Protein Coupled Receptor (MasR). In fibroblasts from patients carrying a BCS1L mutation that impairs complex III (CIII) assembly, CAP-1902 increased mitochondrial turnover by promoting both mitophagy and biogenesis. Specifically, MasR activation triggered the AMPK/ULK1/FUNDC1 mitophagy pathway. Knockdown of FUNDC1 blocked mitophagy but not AMPK activation, confirming pathway specificity. Additionally, a decrease in the occurrence of depolarized mitochondria with treatment indicated the selective targeting of accumulated damaged mitochondria in the disease context. MasR activation by CAP-1902 also stimulated the nuclear translocation of PGC-1, promoting increased expression of transcripts associated with mitochondrial biogenesis, respiratory chain components, and mitochondrial translation. Remarkably, CAP-1902 was ultimately able to restore key defects in CIII-deficient fibroblasts by rescuing bioenergetics and correcting both the aberrant lysosomal distribution and the elevated integrated stress response markers, which is consistent with a shift toward a healthier mitochondrial population. In summary, we describe the first potential GPCR-mediated treatment of mitochondrial diseases and demonstrate that MasR activation by CAP-1902 induces mitochondrial turnover and improves mitochondrial function.

cell biology↗

bioRxiv2021

Lipid Bilayer Induces Contraction of the Denatured State Ensemble of a Helical-Bundle Membrane Protein

Defining the denatured state ensemble (DSE) and intrinsically disordered proteins is essential to understanding protein folding, chaperone action, degradation, translocation and cell signaling. While a majority of studies have focused on water-soluble proteins, the DSE of membrane proteins is much less characterized. Here, we reconstituted the DSE of a helical-bundle membrane protein GlpG of Escherichia coli in native lipid bilayers and measured the DSEs conformation and compactness. The DSE was obtained using steric trapping, which couples spontaneous denaturation of a doubly biotinylated GlpG to binding of two bulky monovalent streptavidin molecules. Using limited proteolysis and mass spectrometry, we mapped the flexible regions in the DSE. Using our paramagnetic biotin derivative and double electron-electron resonance spectroscopy, we determined the dimensions of the DSE. Finally, we employed our Upside model for molecular dynamics simulations to generate the DSE including the collapsed and fully expanded states in a bilayer. We find that the DSE is highly dynamic involving the topology changes of transmembrane segments and their unfolding. The DSE is expanded relative to the native state, but only to 55-90% of the fully expanded condition. The degree of expansion depends on the chemical potential with regards to local packing and the lipid composition. Our result suggests that the E. colis native lipid bilayer promotes the association of helices in the DSE of membrane proteins and, probably in general, facilitating interhelical interactions. This tendency may be the outcome of a general lipophobic effect of proteins within the cell membranes. SignificanceHere, we delineate the conformation of the denatured state ensemble (DSE) of a membrane protein confined in a native lipid bilayer and assay whether the bilayer permits full expansion or nonspecific collapse of the DSE. Using the intramembrane protease GlpG as a model, we find that the denatured state is a dynamic ensemble involving topological changes and local unfolding of transmembrane segments. The bilayer tends to contract the DSE relative to the fully lipid-solvated, expanded conformations while the degree of compactness is determined by the balance between protein-lipid, lipid-lipid and protein-protein interactions. These findings provide new insights into the lipid bilayer as a solvent that mediates folding, chaperone action, turnover and protein-protein interactions in cell membranes.

biophysics↗