Biology subjects

McNamara, H.

Publications and source records attributed to McNamara, H..

2 recordsLinked to original sources

bioRxiv2025

Additivity of the genetic load is a product of both synergistic and antagonistic epistasis in Drosophila

Epistasis has been theoretically implicated in several major evolutionary processes, including the evolution of sex and speciation, but empirical evidence for its impact is still lacking. We tested for epistatic interactions using a full-sib inbreeding design in Drosophila melanogaster. We examined the effects of deleterious mutations on two sequential components of life-history: pupal productivity and pupa-to-adult viability. We observed an accelerating decline in pupal productivity with increasing inbreeding coefficient, consistent with synergistic epistasis, whereas pupa-to-adult viability exhibited a decelerating decline, consistent with antagonistic epistasis. This decoupling led to an overall linear decline in the production of adult offspring with increasing inbreeding. Our findings suggest that epistatic interactions can be highly trait-specific, underscoring the importance of analyzing individual, physiologically interconnected, fitness traits to understand the role of epistasis in evolutionary processes.

evolutionary biology↗

bioRxiv2020

Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal muscle in vitro

Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.

cell biology↗