Biology subjects

Young, R. L.

Publications and source records attributed to Young, R. L..

8 recordsLinked to original sources

bioRxiv2026

From diet to defense: serpin duplication and gene-expression evolution as putative contributors to poison-frog alkaloid sequestration

Diverse organisms use toxins as antipredator defenses. Although many taxa synthesize their toxins, dietary toxin acquisition is less documented, particularly in vertebrates. In poison frogs (Dendrobatidae), efficient sequestration of dietary alkaloids evolved at least three times from ancestors that bore at most trace concentrations of skin alkaloids. Yet molecular mechanisms underlying poison-frog sequestration remain poorly understood. We used two approaches to address this. First, we performed a broad phylogenetic analysis of the serpinA gene family, which includes serpina1-like/alkaloid-binding globulin (ABG), the putative dendrobatid alkaloid transporter, and biliverdin-binding serpins (BBSs), which bind and spectrally tune biliverdin in blue-green arboreal frogs. Second, we used an evolutionarily narrower but discovery-oriented liver gene-expression analysis, contrasting seven populations from two sequestering Epipedobates species, the most recent origin of sequestration among dendrobatids (<15 mya), with two trace-accumulating lineages, Silverstoneia and Hyloxalus. Phylogenetic analyses revealed extensive diversification of ABGs and BBS-like genes in Dendrobatidae, forming two and five major clades, respectively. These expansions reveal broader ligand-binding serpin diversity than previously recognized and indicate that alkaloid sequestration may involve multiple ABG paralogs. Gene-expression analyses revealed 23 candidate genes associated with small-molecule transport, xenobiotic metabolism, and immune response, including serpina1-like, which was overexpressed in Epipedobates. A co-expression network analysis independently placed 20 of the 23 candidates into four key modules (enriched for differentially-expressed genes, containing [≥]1 candidate, and correlated with sequestration). Our findings point to ligand-binding-protein diversification and coordinated gene-expression changes as major contributors to the evolution of alkaloid defenses in poison frogs.

evolutionary biology↗

bioRxiv2026

trAIt: Species-by-Trait Data Retrieval using Large Language Models

Biological research often requires information about species traits. Manual literature collation can be time-consuming and miss parts of the literature. To address this gap, we developed trAIt, a publicly available software for the retrieval of characteristics of species from scientific literature catalogued in the Europe PubMed Central (PubMed) database. trAIt provides a graphical user interface (GUI) in which users specify species and characteristics of interest. Leveraging a large language model (LLM), trAIt retrieves relevant papers, combines their content through a consensus-based summarization model, and outputs a species-by-characteristic table. For a case study involving frog species, trAIt recovered 47.1% of trait-species combinations in 2.75 hours, while an expert curator independently recovered 62.4% over months. The consensus-based summarization substantially aids accuracy compared to single-source extraction. Across three case studies of vertebrate taxa, an expert confirmed the accuracy of 70.9% of trait-species entries recovered by trAIt. We observed considerable variation across taxa in trAIts accuracy, which is possibly due to heterogeneity in open-access literature availability and inconsistencies in species and trait terminology. In sum, our analysis suggests that LLM-based tools can accelerate biological data synthesis but should be used to support domain experts research, rather than replace their judgment.

bioinformatics↗

bioRxiv2026

A pseudoenzyme controls the architecture of the extreme distal tip of motile cilia

Motile cilia are evolutionarily conserved organelles performing essential roles in development and tissue homeostasis. Unlike the core scaffold of motile cilia, the distal regions remain relatively less explored and display great diversity across species. Here, we describe a previously uncharacterized ciliary protein Jhc1, localizing at the extreme distal tip of multiciliated cell (MCC) cilia and encoded only in the genomes of non-mammalian vertebrates. Jhc1 is essential for cilia structure and length in Xenopus, an activity that is conserved in Jhc1 from reptiles and fish. Phylogenetic analysis and structure modeling suggests that Jhc1 arose by duplication and neofunctionalization of thiamine triphosphatase, and we show that residues crucial for that enzymes function have been lost and replaced by new residues essential for ciliary localization. These data provide new insights into the molecular mechanisms underlying the broad diversification of the structures at the tip of motile cilia during evolution.

cell biology↗

bioRxiv2024

Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies

Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, previously socially dominant animals exhibit higher increases in plasma corticosterone and vastly greater transcriptional changes in the medial amygdala (MeA), which is central to the regulation of social behavior, compared to previously subordinate animals. Specifically, social descent is associated with reductions in MeA expression of myelination and oligodendrocyte differentiation genes. Maintaining high social status is associated with high expression of genes related to cholinergic signaling in the MeA. Conversely, social ascent is related to relatively few unique rapid changes in the MeA. We also identify novel genes associated with social transition that show common changes in expression when animals undergo either social descent or social ascent compared to maintaining their status. Two genes, Myosin binding protein C1 (Mybpc1) and -Crystallin (Crym), associated with vasoactive intestinal polypeptide (VIP) and thyroid hormone pathways respectively, are highly upregulated in socially transitioning individuals. Further, increases in genes associated with synaptic plasticity, excitatory glutamatergic signaling and learning and memory pathways were observed in transitioning animals suggesting that adaptations in these processes may support rapid social status changes. Author SummaryWe investigate how male CD-1 mice behaviorally, physiologically, and molecularly respond to changes in their social hierarchies. We found that mice rapidly reform social hierarchies when placed into novel social groups. Formerly dominant mice experience the greatest increase in stress hormone levels and the largest shifts in gene expression in the medial amygdala, a brain region crucial for regulating social behavior. Specifically, we observed reduced expression of genes related to myelin production and maintenance as well as cholinergic functioning in formerly dominant males who socially descended. In contrast, formerly subordinate males who socially ascended displayed fewer genomic changes. Moreover, we identified a set of genes that change expression when animals transition their social status regardless of whether they rise or fall in rank. These social transition genes provide new insights into the biological mechanisms underpinning social plasticity. Our findings demonstrate the distinct molecular mechanisms that are shared between socially ascending versus descending mice, as well as those that are unique to each type of social transition.

neuroscience↗

bioRxiv2021

Distinct inflammatory and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. Particularly, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor energetically inexpensive adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift energy investment in immune functioning and gene expression to match their contextual energetic demands. HighlightsO_LIImmunity is shaped by stress and energetic pressures associated with social status C_LIO_LIDominant and subordinate mice favor adaptive and innate immunity, respectively C_LIO_LIDominants increase expression of genes involved in energy production C_LIO_LIWound healing and DNA repair genes are upregulated in subordinates C_LIO_LIGenes related to maintaining and signaling social status are upregulated in dominants C_LI

immunology↗

bioRxiv2020

Prenatal exposure to EDCs dis-integrates and reconstitutes neuromolecular-behavioral relationships in adult rats

AO_SCPLOWBSTRACTC_SCPLOWExposure to endocrine-disrupting chemicals (EDCs) is ubiquitous in all species, including humans. Previous studies have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs [polychlorinated biphenyls (PCB), an industrial chemical mixture; vinclozolin (VIN), a fungicide], or vehicle. In adulthood, a sociosexual preference test (choice between hormone-primed and hormone-depleted opposite-sex rats) was administered. We profiled gene expression of in three brain regions involved in these behaviors [preoptic area (POA), medial amygdala (MeA), ventromedial nucleus (VMN)]. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region (POA, MeA, VMN) had unique sets of genes altered in a sex- and EDC-specific manner. Sexually dimorphic gene expression disruption was particularly prominent for gene modules pertaining to sex steroid hormones and nonapeptides in the MeA. EDC exposure also changed the relationships between gene expression and behavior in the mate preference test, a pattern we refer to as dis-integration and reconstitution. These findings underscore the profound effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of mate preference behavior after prenatal exposure to EDCs.

neuroscience↗

bioRxiv2020

Mapping Functional Protein Neighborhoods in the Mouse Brain

New proteomics methods make it possible to determine protein interaction maps at the proteome scale without the need for genetically encoded tags, opening up new organisms and tissue types to investigation. Current molecular and computational methods are oriented towards protein complexes that are soluble, stable, and discrete. However, the mammalian brain, among the most complicated and most heavily studied tissue types, derives many of its unique functions from protein interactions that are neither discrete nor soluble. Proteomics investigations into the global protein interaction landscape of the brain have therefore leveraged non-proteomics datasets to supplement their experiments. Here, we develop a novel, integrative proteomics pipeline and apply it to infer a global map of functional protein neighborhoods in the mouse brain without the aid of external datasets. By leveraging synaptosome enrichment and interactomics methods that target both soluble and insoluble protein fractions, we resolved protein interactions for key neural pathways, including those from refractory subcellular fractions such as the membrane and cytoskeleton. In comparison to external datasets, our observed interactions perform similarly to hand-curated synaptic protein interactions while also suggesting thousands of novel connections. We additionally employed cleavable chemical cross-linkers to detect direct binding partners and provide structural context. Our combined map suggests new protein pathways and novel mechanisms for proteins that underlie neurological diseases, including autism and epilepsy. Our results show that proteomics methods alone are sufficient to determine global interaction maps for proteins that are of broad interest to neuroscience. We anticipate that our map will be used to prioritize new research avenues and will pave the way towards future proteomics techniques that resolve protein interactions at ever greater resolution.

systems biology↗

bioRxiv2019

Comparative transcriptomics reveal distinct patterns of gene expression conservation through vertebrate embryogenesis

Despite lifes diversity, studies of variation across animals often remind us of our shared evolutionary past. Abundant genome sequencing over the last ~25 years reveals remarkable conservation of genes and recent analyses of gene regulatory networks illustrate that not only genes but entire pathways are conserved, reused, and elaborated in the evolution of diversity. Predating these discoveries, 19th-century embryologists observed that though morphology at birth varies tremendously, certain stages of embryogenesis appear remarkably similar across vertebrates. Specifically, while early and late stages are variable across species, anatomy of mid-stages embryos (the phylotypic stage) is conserved. This model of vertebrate development and diversification has found mixed support in recent analyses comparing gene expression across species possibly owing to differences across studies in species, embryonic stages, and gene sets compared. Here we perform a comparative analysis using 186 microarray and RNA-seq expression data sets covering embryogenesis in six vertebrate species spanning ~420 million years of evolution. We use an unbiased clustering approach to group stages of embryogenesis by transcriptomic similarity and ask whether gene expression similarity of clustered embryonic stages deviates from the null hypothesis of no relationship between timing and diversification. We use a phylogenetic comparative approach to characterize expression conservation pattern (i.e., early conservation, hourglass, inverse hourglass, late conservation, or no relationship) of each gene at each evolutionary node. Across vertebrates, we find an enrichment of genes exhibiting early conservation, hourglass, late conservation patterns and a large depletion of gene exhibiting no distinguishable pattern of conservation in both microarray and RNA-seq data sets. Enrichment of genes showing patterned conservation through embryogenesis indicates diversification of embryogenesis may be temporally constrained. However, the circumstances (e.g., gene groups, evolutionary nodes, species) under which each pattern emerges remain unknown and require both broad evolutionary sampling and systematic examination of embryogenesis across species.

evolutionary biology↗