Biology subjects

Ross, J. A.

Publications and source records attributed to Ross, J. A..

3 recordsLinked to original sources

bioRxiv2022

Exercise induces myonuclear remodelling in humans independently of age

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with nuclear lamina protein Lamin A regulating nuclear shape, nuclear mechanics, and ultimately gene expression. Defective Lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals. Complementary to this, exercise resulted in increased levels of Lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. Key pointsO_LIThe nucleus plays an active role in translating forces into biochemical signals C_LIO_LIMyonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. C_LIO_LIHere, we present striking differences in myonuclear shape and mechanics associated with exercise, in both young and old humans. C_LIO_LIMyonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals. C_LIO_LIWe conclude that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan. C_LI

cell biology↗

bioRxiv2019

Assembly of a young vertebrate Y chromosome reveals convergent signatures of sex chromosome evolution

Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to rapid degeneration of the Y chromosome. However, these early stages of degeneration are not well understood, as complete Y chromosome sequence assemblies have only been generated across a handful of taxa with ancient sex chromosomes. Here we describe the assembly of the threespine stickleback (Gasterosteus aculeatus) Y chromosome, which is less than 26 million years old. Our previous work identified that the non-recombining region between the X and the Y spans [~]17.5 Mb on the X chromosome. Here, we combined long-read PacBio sequencing with a Hi-C-based proximity guided assembly to generate a 15.87 Mb assembly of the Y chromosome. Our assembly is concordant with cytogenetic maps and Sanger sequences of over 90 Y chromosome clones from a bacterial artificial chromosome (BAC) library. We found three evolutionary strata on the Y chromosome, consistent with the three inversions identified by our previous cytogenetic analyses. The young threespine stickleback Y shows convergence with older sex chromosomes in the retention of haploinsufficient genes and the accumulation of genes with testis-biased expression, many of which are recent duplicates. However, we found no evidence for large amplicons found in other sex chromosome systems. We also report an excellent candidate for the master sex-determination gene: a translocated copy of Amh (Amhy). Together, our work shows that the same evolutionary forces shaping older sex chromosomes can cause remarkably rapid changes in the overall genetic architecture on young Y chromosomes.

evolutionary biology↗

bioRxiv2019

Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy

Nemaline myopathy (NM) is a genetically heterogeneous skeletal muscle disorder caused by mutations predominately affecting contractile filaments, in particular thin filament structure and/or regulation. The underlying cellular pathophysiology of this disease remains largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mice and patients with NM, including disrupted nuclear envelope, altered chromatin arrangement, and disorganisation of the cortical cytoskeleton. We demonstrate that such nuclear defects are caused by impairment of muscle fibre contractility, and that cytoskeletal organisation determines nuclear morphology. Our results overlap with findings in diseases caused by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to underlie some of the hallmarks of NM, which include broad transcriptional alterations, arrested muscle fibre growth, contractile filament disarray and altered mechanical properties.

cell biology↗