Biology subjects

Weaver, R. J.

Publications and source records attributed to Weaver, R. J..

6 recordsLinked to original sources

bioRxiv2026

Loss of neurofibromin alters adult metabolism via effects during a developmental critical period

Metabolic alterations commonly accompany neurodevelopmental disorders and may contribute to their pathophysiology. Neurofibromatosis type 1 (OMIM 162200) is a genetic disorder that results from mutations in the NF1 gene and its encoded neurofibromin protein (Nf1). The disorder is multisystemic, affecting multiple aspects of development, physiology, and brain function. In addition, recent evidence suggests that Nf1 deficiency alters metabolic function in both humans and animal models. Whether the metabolic alterations result from changes in neurodevelopment is not known. Here we approach this question in Drosophila melanogaster, which expresses a conserved NF1 gene, exhibits phenotypes reminiscent of the human disease, and shares key developmental mechanisms with humans. Flies with nf1 mutations or RNAi-mediated knockdown exhibit altered metabolism in adulthood. Conditional Nf1 inactivation revealed that the adult metabolic phenotype resulted from loss of Nf1 in neurons during a developmental critical period (third instar larva/pupa), which corresponded to the period of nervous system maturation. Prior to the developmental critical period, nf1 mutants did not exhibit metabolic difference - rather, the metabolic alterations appeared only after the critical period. This suggests that the adult phenotype results from the onset of the developmental alteration during the critical period. High-resolution respirometry on adult mitochondria revealed no differences in complex I/II function or fatty acid oxidation between nf1 mutants and controls, suggesting that the metabolic alterations localize upstream of the electron transport chain at the cellular level. Overall, these data suggest that loss of Nf1 alters adult metabolism via effects during a critical period of nervous system development.

neuroscience↗

bioRxiv2026

Horizontally acquired mitochondrial alternative oxidase contributes to springtail bioenergetics and life belowground

Springtails are tiny hexapods that occupy habitats ranging from above the soil surface to hypoxia-prone belowground environments, yet the physiological mechanisms enabling this ecological expansion have remained unresolved. Here, I take an evolutionary bioenergetics approach to show that a mitochondrial alternative oxidase (AOX) acquired by horizontal gene transfer in the springtail ancestor became functionally integrated into animal physiology and was preferentially retained in lineages occupying low-oxygen habitats. Surveying 202 springtail genome assemblies, I identified 65 high-confidence AOX loci in 48 species, each embedded within otherwise typical springtail genomic neighborhoods. Phylogenetic and motif-based analyses support an oomycete donor and indicate ancestral acquisition followed by repeated loss, especially in aboveground taxa. High-resolution respirometry and hypoxia-exposure experiments further show that AOX is active only in AOX-positive species and is associated with hypoxia tolerance. These results identify horizontal gene transfer as a source of ecophysiological innovation in animals and suggest that acquired mitochondrial functions can help shape ecological sorting across environmental gradients, with implications for soil ecosystem processes. Significance StatementHorizontal gene transfer can introduce new genes into animal genomes, but few cases connect gene origin to physiology and ecology. Springtails are abundant soil mesofauna that help define ecological systems and nutrient flux yet physiological challenges that subterranean environments impose raise questions regarding the mechanisms of adaptation to life below ground. This study shows that springtails acquired mitochondrial alternative oxidase (AOX), a respiratory enzyme widely associated with stress tolerance in plants, fungi, protists, and some animals, from an oomycete donor early in their evolutionary history and that AOX has been retained in hypoxia-tolerant species and incorporated it into the physiology as a potential mechanism for tolerance of belowground conditions. These findings link macroevolutionary patterns to bioenergetic processes that help shape ecological distribution and tolerance of environmental stressors, with implications for biodiversity and ecosystem function.

evolutionary biology↗

bioRxiv2022

Disentangling positive vs. relaxed selection in animal mitochondrial genomes

Disentangling different types of selection is a common goal in molecular evolution. Elevated dN/dS ratios (the ratio of nonsynonymous to synonymous substitution rates) in focal lineages are often interpreted as signs of positive selection. Paradoxically, relaxed purifying selection can also result in elevated dN/dS ratios, but tests to distinguish these two causes are seldomly implemented. Here, we reevaluated seven case studies describing elevated dN/dS ratios in animal mtDNA and their accompanying hypotheses regarding selection. They included flightless vs. flighted lineages in birds, bats, and insects, and physiological adaptations in snakes, two groups of electric fishes, and primates. We found that elevated dN/dS ratios were often not caused by the predicted mechanism, and we sometimes found strong support for the opposite mechanism. We discuss reasons why energetic hypotheses may be confounded by other selective forces acting on mtDNA and caution against overinterpreting molecular "spandrels", including elevated dN/dS ratios.

evolutionary biology↗

bioRxiv2021

Fatty acid binding proteins shape the cellular response to activation of the glucocorticoid receptor

Glucocorticoids are steroid hormones that are essential for life in mammals. Therapeutically, they are some of the most cost-effective drugs for the treatment of inflammatory diseases ranging from skin rashes to COVID-19, but their use is limited by adverse effects. Glucocorticoids exert their effects via the glucocorticoid receptor, a type I nuclear hormone receptor which modulates gene expression. The transcriptional activity of some related, but nuclear restricted, type II nuclear hormone receptors can be enhanced by a family of intracellular transport proteins, the fatty acid binding proteins (FABPs). We find that the transcriptional activity of the GR can be altered by a sub-set of FABP family members dependent on the GR-ligand. The ability of some FABPs to selectively promote or limit the transcriptional activity of the GR in a ligand-dependent manner could facilitate the discovery of drugs that narrow GR activity to only the desired subset of therapeutically relevant genes.

pharmacology and toxicology↗

bioRxiv2019

A genomic analysis and transcriptomic atlas of gene expression in Psoroptes ovis reveals feeding- and stage-specific patterns of allergen expression

Psoroptic mange, caused by infestation with the ectoparasitic mite, Psoroptes ovis, is highly contagious, resulting in intense pruritus and represents a major welfare and economic concern for the livestock industry Worldwide. Control relies on injectable endectocides and organophosphate dips, but concerns over residues, environmental contamination, and the development of resistance threaten the sustainability of this approach, highlighting interest in alternative control methods. However, development of vaccines and identification of chemotherapeutic targets is hampered by the lack of P. ovis transcriptomic and genomic resources. Building on the recent publication of the P. ovis draft genome, here we present a genomic analysis and transcriptomic atlas of gene expression in P. ovis revealing feeding- and stage-specific patterns of gene expression, including novel multigene families and allergens. Network-based clustering revealed 14 gene clusters demonstrating either single- or multi-stage specific gene expression patterns, with 3,075 female-specific, 890 male-specific and 112, 217 and 526 transcripts showing larval, protonymph and tritonymph specific-expression, respectively. Detailed analysis of P. ovis allergens revealed stage-specific patterns of allergen gene expression, many of which were also enriched in \"fed\" mites and tritonymphs, highlighting an important feeding-related allergenicity in this developmental stage. Pair-wise analysis of differential expression between life-cycle stages identified patterns of sex-biased gene expression and also identified novel P. ovis multigene families including known allergens and novel genes with high levels of stage-specific expression. The genomic and transcriptomic atlas described here represents a unique resource for the acarid-research community, whilst the OrcAE platform makes this freely available, facilitating further community-led curation of the draft P. ovis genome.

genomics↗

bioRxiv2017

On the bioconversion of dietary carotenoids to astaxanthin and its distribution in the marine copepod, Tigriopus californicus

Red carotenoid-based coloration is widely distributed across marine and terrestrial animals and has taken a prominent role in studies of how phenotypic traits evolve in response to natural and sexual selection. Key to these studies is an understanding of the physiological mechanisms that give rise to red coloration, yet an ideal model system for such work has not been identified. The red marine copepod Tigriopus californicus is used as a model system for studies in ecotoxicology, genetics, and physiology, but the mechanisms involved in its bright red coloration have not been well studied. Like nearly all animals that display red carotenoid coloration, T. californicus likely convert yellow carotenoids present in their algal diet to red carotenoids. We conducted precursor/product feeding experiments to demonstrate that T. californicus bioconverts dietary carotenoids to the red carotenoid, astaxanthin. In separate treatment groups, copepods were fed carotenoids that are precursors to specific astaxanthin bioconversion pathways. We found that copepods from each precursor pigment group produced astaxanthin, and that the amount produced depended on which carotenoid was supplemented. We also describe the distribution of astaxanthin in developing egg sacs and show that the red color of the naupliar eyespot is not due to astaxanthin. We briefly discuss the potential of Tigriopus californicus to serve as a model system for the study of carotenoid metabolism in animals.

zoology↗