Biology subjects

Yi, X.

Publications and source records attributed to Yi, X..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Biphasic bactericidal activity of nitroxoline against Acinetobacter baumannii isolates from urinary tract infections

Acinetobacter baumannii is a critical pathogen which can cause hospital-acquired infections, particularly urinary tract infections (UTIs). The antimicrobial resistance (AMR) of A. baumannii is rising which poses a significant challenge to clinical management. Nitroxoline, an old antibiotic for treating uncomplicated UTIs, has gained renewed interest as a potential therapeutic option. Here, we investigates the bactericidal activity of nitroxoline against 34 A. baumannii (17 carbapenem-resistant and 17 carbapenem-sensitive isolates) collected from UTI patients. Nitroxoline exhibited a biphasic bactericidal effect, characterized by enhanced efficacy up to an optimal bactericidal concentration (OBC), followed by declined activity at higher nitroxoline concentrations. The OBCs, minimum bactericidal concentration (MBC), minimum inhibitory concentration (MIC), and time-killing curves were evaluated to elucidate bactericidal activity. Raman deuterium stable isotope probing (Raman-DIP) was employed to validate nitroxolines bactericidal effect and its impact on bacterial metabolic activity and survival rates. These results demonstrate that nitroxoline exhibits excellent inhibitory and bactericidal activity against A. baumannii. While nitroxoline exhibits biphasic bactericidal activity with OBC50/90 values of 4/8 mg/L. Raman spectroscopy identified a decreased C-D ratio as nitroxoline concentration increased, indicating reduced metabolic activity. Notably, an inverse correlation (r = -0.7594, p <0.0001) was observed between bacterial survival and the ccratio at concentrations above the OBC. These findings underscore the necessity of optimizing dosing regimens to enhance nitroxolines therapeutic efficacy and alleviate AMR development. Raman-DIP emerges as a robust tool for assessing nitroxolines effects on bacterial metabolism and determining MIC, offering valuable insights for future clinical applications.

microbiology↗

bioRxiv2025

deepTFBS: Improving within- and cross-species prediction of transcription factor binding using deep multi-task and transfer learning

The precise prediction of transcription factor binding sites (TFBSs) is crucial in understanding gene regulation. In this study, we present deepTFBS, a comprehensive deep learning (DL) framework that builds a robust DNA language model of TF binding grammar for accurately predicting TFBSs within and across plant species. Taking advantages of multi-task DL and transfer learning, deepTFBS is capable of leveraging the knowledge learned from large-scale TF binding profiles to enhance the prediction of TFBSs under small-sample training and cross-species prediction tasks. When tested using available information on 359 Arabidopsis TFs, deepTFBS outperformed previously described prediction strategies, including position weight matrix, deepSEA and DanQ, with a 244.49%, 49.15%, and 23.32% improvement of the area under the precision-recall curve (PRAUC), respectively. Further cross-species prediction of TFBS in wheat showed that deepTFBS yielded a significant PRAUC improvement of 30.6% over these three baseline models. deepTFBS can also utilize information from gene conservation and binding motifs, enabling efficient TFBS prediction in species where experimental data availability is limited. A case study, focusing on the WUSCHEL (WUS) transcription factor, illustrated the potential use of deepTFBS in cross-species applications, in our example between Arabidopsis and wheat. deepTFBS is publically available at https://github.com/cma2015/deepTFBS. One sentence summaryThe high-performing deep learning framework deepTFBS can flexibly perform within- and cross-species prediction of TF binding, transferring the transcription regulation from model to non-model species.

bioinformatics↗

bioRxiv2025

Comprehensive phylogenetic reconstructions support ancestral omnivory in the ecologically diverse bat family Phyllostomidae

Adaptive radiations often occur with an early burst of ecological diversification, which requires not only various available niches but also a generalist ancestor with wide ecological niche breadths. However, ancestral generalism remains hard to test in empirical cases. The New World leaf-nosed bats (family Phyllostomidae) represent an unparalleled mammalian adaptive radiation with diverse dietary niches including arthropods, blood, terrestrial vertebrates, nectar, and fruits. However, when and how often phyllostomid bats transitioned from insectivory to fruit or nectar feeding remains unclear. Here we tested the hypotheses of ancestral insectivory versus ancestral omnivory in Phyllostomidae (141 species) using improved trait reconstructions based on multi-response phylogenetic threshold models, while explicitly accounting for phylogenetic uncertainty. Our results indicate that complementary fruit feeding has fully evolved at the early burst of the phyllostomid radiation and started to evolve in the most recent common ancestor of the family, supporting the ancestral omnivory hypothesis. In addition, fruit feeding probably evolved before nectar eating in Phyllostomidae, in contrast to the claims of previous studies. Extending this analysis to all bat families (621 species) reveals independent evolution of ancestral fruit feeding in four families, namely the Pteropodidae (Old World fruit bats) and three families from the Noctilionoidea superfamily. Despite the ancestral omnivory of these fruit-eating families, only Phyllostomidae and Pteropodidae show high species diversity and evolved predominant and strict fruit feeding. Therefore, our results reveal that ancestral generalism (i.e., omnivory) may be a precondition of but does not necessarily lead to adaptive radiations which also require subsequent niche partitioning and speciation.

evolutionary biology↗

bioRxiv2024

ER stress relief drives beta cell proliferation

Regenerating endogenous pancreatic {beta}-cells is a potentially curative yet currently elusive strategy for diabetes therapy. Mimicking the microenvironment of the developing pancreas and leveraging vascular signals that support pancreatic endocrinogenesis may promote {beta}-cell regeneration. We aimed to investigate whether recovery from experimental hypovascularization of the endocrine pancreas, achieved by modulating the transgenic production of a VEGF-A blocker in {beta}-cells, could trigger mouse {beta}-cell proliferation. Serendipitously, we found that transgene overexpression in {beta}-cells induces endoplasmic reticulum (ER) stress and that subsequent relief from this stress stimulates {beta}-cell proliferation independent of vessel recovery. Transient GFP overexpression in vivo and chemical induction of ER stress in vitro replicated this {beta}-cell cycling response. Our findings highlight the potential side effects of ER stress due to transgene overexpression in {beta}-cells and assert that ER stress relief serves as a potent regenerative stimulus.

molecular biology↗

bioRxiv2024

Identifying Causal Relations between Gut Microbiome, Metabolic Dysfunction-Associated Fatty Liver Disease and the Novel Mediators of Blood Metabolites

BackgroundResearch has established connection between gut microbiome and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the causal relationships and the roles of potential mediating factors, such as blood metabolites, remain unclear. MethodsWe conducted a bidirectional and mediation Mendelian randomization (MR) study using the genome-wide summary statistics of gut microbial taxa (Dutch Microbiome Project, n = 7,738), blood lipids (UK Biobank, n =8,299), and the largest MAFLD GWAS data (1,483 cases and 17,781 controls). We used the inverse-variance weighted estimation method as our primary approach. The multivariable Mendelian randomization (MVMR) and two-step MR approaches were used to prioritize the most likely causal metabolites as mediators. Additionally, we conducted linkage disequilibrium score regression (LDSC) analyses to assess genetic correlations, and downstream gene-based analyses to investigate the shared biological mechanism. ResultsBy testing the causal effects of 205 bacterial pathways and 207 taxa on MAFLD, we identified 5 microbial taxa causally associated with MAFLD, notably the species Parabacteroides merdae (OR [95%CI] = 1.191[1.022-1.388], p = 0.025). Among 1,399 blood metabolites, 53 showed causal associations with MAFLD, with pregnenetriol sulfate identified as a mediator for genus Parabacteroides on MAFLD (proportion mediated = 16.30%). LDSC analysis also provided suggestive evidence for a potential genetic correlation between them (rg= 2.124, p=0.009). ConclusionsThe study suggested a novel causal relationship between gut microbial taxa and MAFLD, especially the genus Parabacteroides merdae and blood metabolite pregnenetriol sulfate might mediate this relationship. ImportanceOur study reveals novel insights into how the intersection of microorganisms living in the human gut, known as the gut microbiome, influences the development of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a condition increasingly recognized as a major global health concern. By identifying specific gut microbiome taxa and metabolites that contribute to the onset and progression of MAFLD, our findings enhance comprehension of this prevalent condition and unveil promising prospects for its prevention and intervention. We discovered that certain gut bacteria can affect the levels of blood metabolites, which in turn impact the livers health. This work carries significant implications for novel strategies for MAFLD prevention and treatment, including interventions aimed at modifying the gut microbiome. Our research underscores the gut-liver connection and its implications for metabolic diseases, contributing to future therapeutic developments that could improve public health worldwide. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=158 HEIGHT=200 SRC="FIGDIR/small/606637v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1b16347org.highwire.dtl.DTLVardef@ecf53eorg.highwire.dtl.DTLVardef@d8cb5borg.highwire.dtl.DTLVardef@10efe44_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Stratifying variant deleteriousness and trait-modulating effect under human recent adaptation

Despite advances in annotating and interpreting human genetic variants, existing methods to distinguish deleterious/pathogenic from neutral variants still inadequately capture the nuanced impact of genetic variants on fitness and disease susceptibility. In this study, we introduced a new deep learning framework, the FIND model, by stratifying genetic variants into refined categories based on selection pressures and derived allele frequency. FIND demonstrated superior performance over existing genome-wide methods, delivering enhanced resolution in differentiating trait-modulating alleles from those that are pathogenic or neutral. Access to base-wise informative annotations has unveiled novel features that significantly enhance the model interpretability, and FIND has adeptly delineated evolutionary trends in human accelerated regions. Furthermore, applying FIND to the interpretation of clinical variants demonstrates its substantial potential in reclassifying variants of unknown significance. This work advances our understanding of the genetic underpinnings of human adaptation and disease, providing a new tool to explore the complexities of genetic contributions to health.

genetics↗

bioRxiv2024

Individual differences in the expression and control of anger are encoded in the same fronto-temporal GM-WM network

Anger can be deconstructed into distinct components: a temporary emotional state (state anger), a stable personality trait (trait anger), a tendency to outwardly express it (anger-out), or to internally suppress it (anger-in), and the capability to manage it (anger control). These aspects exhibit individual differences that vary across a continuum. Notably, the capacity to express and control anger are of great importance to modulate our reactions in interpersonal situations. The aim of this study was to test the hypothesis that anger expression and control are negatively correlated and that both can be decoded by the same patterns of grey and white matter features of a fronto-temporal brain network. To this aim, a data fusion unsupervised machine learning technique, known as transposed Independent Vector Analysis (tIVA), was used to decompose the brain into covarying GM-WM networks and then backward regression was used to predict both anger expression and control from a sample of 212 healthy subjects. Confirming our hypothesis, results showed that anger control and anger expression are negatively correlated, the more individuals control anger, the less they externalize it. At the neural level, individual differences in anger expression and control can be predicted by the same GM-WM network. As expected, this network included fronto-temporal regions as well as the cingulate, the insula and the precuneus. The higher the concentration of GM-WM in this brain network, the higher level of externalization of anger, and the lower the anger control. These results expand previous findings regarding the neural bases of anger by showing that individual differences in anger control and expression can be predicted by morphometric features.

neuroscience↗

bioRxiv2024

Neuropeptide Y co-opts neuronal ensembles for memory lability and stability

Memory engrams are formed by activity-dependent recruitment of distinct subsets of excitatory principal neurons (or neuronal ensembles) whereas inhibitory neurons pivot memory lability and stability1-5. However, the molecular logic for memory engrams to preferentially recruit specific type of interneurons over other subtypes remains enigmatic. Using activity-dependent single-cell transcriptomic profiling6-8 in mice with training of cued fear memory and extinction, we discovered that neuropeptide Y (NPY)-expressing (NPY+) GABAergic interneurons in the ventral hippocampal CA1 (vCA1) region exert fast GABAergic inhibition to facilitate the acquisition of memory, but bifurcate NPY-mediated slow peptidergic inhibition onto distinct sub-ensembles underlying the extinction of single memory trace. Genetically encoded calcium and NPY sensors revealed that both calcium dynamics of NPY+ neurons and their NPY release in vCA1 ramp up as extinction learning progresses while behavioral state switches from "fear-on" to "fear-off". Bidirectional manipulations of NPY+ neurons or NPY itself demonstrated NPY is both necessary and sufficient to control the rate and degree of memory extinction by acting on two physically non-overlapping sub-ensembles composed of NPY1R- and NPY2R-expressing neurons. CRISPR/Cas9-mediated knockout of NPY2R or NPY1R further unravels that NPY co-opts its actions on these two sub-ensembles to gate early fast and late slow stages of extinction. These findings exemplify the intricate spatiotemporal orchestration of slow peptidergic inhibitions from single subtype of GABAergic interneurons to fine-tune engram lability verse stability of memory.

neuroscience↗

bioRxiv2024

An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

neuroscience↗

bioRxiv2024

SLRfinder: a method to detect candidate sex-linked regions with linkage disequilibrium clustering

Despite their critical roles in genetic sex determination, sex chromosomes remain unknown in many non-model organisms. In contrast to conserved sex chromosomes in mammals and birds, studies of fish, amphibians, and reptiles have found highly labile sex chromosomes with newly evolved sex-linked regions (SLRs). These labile sex chromosomes are important for understanding early sex chromosome evolution but are difficult to identify due to the lack of Y/W degeneration and SLRs limited to small genomic regions. Here we present SLRfinder, a method to identify candidate SLRs and labile sex chromosomes using linkage disequilibrium (LD) clustering, patterns of heterozygosity, and genetic divergence. SLRfinder does not rely on specific sequencing methods or reference genomes and does not require phenotypic sexes which may be unknown from population sampling, although sex information can be incorporated to provide additional inference on candidate SLRs. We tested SLRfinder using various published datasets and compared it to SATC, a method that identifies sex chromosomes based on the depth of coverage and also does not require phenotypic sex. Results show that SATC works better on conserved sex chromosomes (e.g., in African leopards), whereas SLRfinder outperforms SATC in analyzing labile sex chromosomes (e.g., in nine-spined sticklebacks and chum salmon). Since SLRfinder primarily relies on LD clusters, it is expected to be most sensitive to the SLRs harboring structural variants (e.g., inversion) due to strongly reduced recombination rates in heterozygotes. SLRfinder provides a novel and complementary approach for identifying SLRs and uncovering additional sex chromosome diversity in nature.

genomics↗

bioRxiv2024

Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy

The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, we show that self-assembled peptide amphiphile (PA) nanostructures can dynamically interact with endogenous biomolecules and take advantage of naturally occurring processes to target a broad range of solid tumors. In circulation, self-assembled PA nanostructures disassemble and reassemble mainly with lipoproteins, which prolongs blood circulation and dramatically improves tumor accumulation and retention. Mechanistic studies suggested that PAs internalize into cancer cells by assembling with their cell membranes and independently of specific receptors. By exploiting these interactions, a PA developed in this study (namely SA-E) demonstrated specific accumulation in various xenograft, syngeneic, patient-derived xenograft, or transgenic rodent models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer imaging and therapy.

bioengineering↗

bioRxiv2023

Sex chromosome turnover in hybridizing stickleback lineages

Recent discoveries of sex chromosome diversity across the tree of life have challenged the canonical model of conserved sex chromosome evolution and evoked new theories on labile sex chromosomes that maintain less differentiation and undergo frequent turnover. However, theories of labile sex chromosome evolution lack direct empirical support due to the paucity of case studies demonstrating ongoing sex chromosome turnover in nature. Two divergent lineages (viz. WL & EL) of nine-spined sticklebacks (Pungitius pungitius) with different sex chromosomes (linkage group [LG] 12 in the EL, unknown in the WL) hybridize in a natural secondary contact zone in the Baltic Sea, providing an opportunity to study ongoing turnover between coexisting sex chromosomes. We first identified an 80 kbp genomic region on LG3 as the sex-determining region (SDR) using whole-genome resequencing data of family crosses. We then verified this region as the SDR in most other WL populations and demonstrated an ongoing sex chromosome turnover in admixed marine populations where the evolutionarily younger and homomorphic LG3 sex chromosomes replace the older and heteromorphic LG12 sex chromosomes. The results provide a rare glimpse of ongoing sex chromosome turnover and indicate possible existence of additional but yet undiscovered sex chromosome diversity in Pungitius sticklebacks. TeaserEvolutionarily young sex chromosomes replace the older ones in the hybrid zone of European Pungitius stickleback lineages.

evolutionary biology↗

bioRxiv2023

Suppression of the Integrated Stress Response in Islet β Cells Decreases Risk of Autoimmune Diabetes

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eIF2. In T1D, maladaptive unfolded protein response (UPR) in insulin-producing {beta} cells renders these cells susceptible to autoimmunity. We show that inhibition of the eIF2 kinase PERK, a common component of the UPR and ISR, reverses the mRNA translation block in stressed human islets and delays the onset of diabetes, reduces islet inflammation, and preserves {beta} cell mass in T1D-susceptible mice. Single-cell RNA sequencing of islets from PERK-inhibited mice shows reductions in the UPR and PERK signaling pathways and alterations in antigen processing and presentation pathways in {beta} cells. Spatial proteomics of islets from these mice shows an increase in the immune checkpoint protein PD-L1 in {beta} cells. Golgi membrane protein 1, whose levels increase following PERK inhibition in human islets and EndoC-{beta}H1 human {beta} cells, interacts with and stabilizes PD-L1. Collectively, our studies show that PERK activity enhances {beta} cell immunogenicity, and inhibition of PERK may offer a strategy to prevent or delay the development of T1D.

cell biology↗

bioRxiv2023

NanoLAS: a Comprehensive Nanobody Database with Data Integration, Consolidation, and Application

Nanobodies, a unique subclass of antibodies first discovered in camelid animals, are composed solely of a single heavy chains variable region (VHH). Their significantly reduced molecular weight, in comparison to conventional antibodies, confers numerous advantages in the treatment of various diseases. As research and applications involving nanobodies expand, the quantity of identified nanobodies is also rapidly growing. However, the existing antibody databases are deficient in type and coverage, failing to satisfy the comprehensive needs of researchers and thus, impeding progress in nanobody research. In response to this, we have amalgamated data from multiple sources to successfully assemble a new and comprehensive nanobody database. This database has currently included the latest nanobody data, provides researchers with an excellent search and data display interface, thus facilitating the progression of nanobody research and their application in disease treatment. In summary, the newly constructed Nanobody Library and Archive System (NanoLAS) may significantly enhance the retrieval efficiency and application potential of nanobodies. We envision that NanoLAS will serve as an accessible, robust, and efficient tool for nanobody research and development, propelling advancements in the field of biomedicine. Database URLhttps://www.nanolas.cloud

bioinformatics↗

bioRxiv2023

Improved dual-color GRAB sensors for monitoring dopaminergic activity in vivo

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in freely moving mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDA sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.

neuroscience↗

bioRxiv2023

Inferring the Hoxa1 Gene Regulatory Network in Mouse Embryonic Stem Cells: Time-Series RNA-seq Data and Computational Modeling Approach

The homeotic gene Hoxa1 plays a pivotal role in regulating embryonic pattern formation and morphogenesis during mouse embryogenesis. However, despite the identification of a number of putative Hoxa1 target genes, the intricate regulatory relationships between these targets remain largely elusive. Leveraging the advancements in high-throughput technologies and sophisticated computational methods, we aimed to infer the Gene Regulatory Networks (GRNs) governed by Hoxa1 that direct cellular function, morphology, and/or differentiation. To achieve this, we generated time-series RNA-seq data from Retinoic Acid (RA)-treated Wild Type versus Hoxa1-null mouse ES cells, enabling the construction of the Hoxa1 GRN. To create this GRN, we employed NARROMI, a published technique known for its noise reduction capabilities and improved accuracy in gene-regulation inference. Using this technique, we identified putative direct and indirect connections between Hoxa1 and a set of genes with known relevance in embryonic development. Validation through qPCR confirmed the Hoxa1-dependence on mRNA expression for selected genes, both within the immediate vicinity (direct) and in secondary interactions (indirect). Furthermore, by mapping the candidate genes to relevant Gene Ontology (GO) networks, we verified their involvement in processes likely regulated by Hoxa1. Our findings provide compelling evidence supporting the accuracy of the NARROMI analysis in generating a hierarchical network of genes under the transcriptional control of Hoxa1 Transcription Factor (TF), specifically in mouse ES cells. This network reveals a pool of promising candidate genes that may function as direct targets of Hoxa1. However, further investigations, including the characterization of Hoxa1 protein interactions with target loci DNA, are necessary to confirm their direct regulatory relationship with this TF. Moreover, the time-series RNA-seq data from Wild Type ES cells, coupled with the methodology employed in this study, hold the potential for constructing GRNs for additional TFs activated by RA. This comprehensive approach can shed further light on the intricate regulatory networks governing cellular function, morphology, and differentiation, advancing our understanding of embryonic development and gene regulation processes.

bioinformatics↗

bioRxiv2023

Interferons are the key cytokines acting on pancreatic islets in type 1 diabetes

The pro-inflammatory cytokines IFN, IFN{gamma}, IL-1{beta} and TNF may contribute to innate and adaptive immune responses during islet inflammation (insulitis) in type 1 diabetes (T1D). We used deep RNA-sequencing analysis to characterize the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by T1D. IFN and IFN{gamma} had a much greater impact on the beta cell transcriptome when compared to IL-1{beta} and TNF. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from T1D patients, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to "danger signals" such as viral infections. These data suggest that IFN and IFN{gamma} are the central cytokines at the islet level in T1D, contributing to the triggering and amplification of autoimmunity.

immunology↗

bioRxiv2023

Heterogeneous genomic architecture of skeletal armour traits in sticklebacks

Whether populations adapt to similar selection pressures using the same underlying genetic variants depends on population history and the distribution of standing genetic variation at the metapopulation level. Studies of sticklebacks provide a case in point: when colonising and adapting to freshwater habitats, three-spined sticklebacks (Gasterosteus aculeatus; TSSs) with high gene flow tend to fix the same adaptive alleles in the same major loci, whereas nine-spined sticklebacks (Pungitius pungitius; NPSs) with limited gene flow tend to utilize a more heterogeneous set of loci. In accordance with this, we report results of quantitative trait locus (QTL) analyses using a F2 back-cross design showing that lateral plate number variation in the western European lineage of NPSs mapped to three moderate-effect QTL, contrary to one major QTL in TSSs and these QTL were different from the four previously identified QTL in the eastern European lineage of NPSs. Furthermore, several QTL were identified associated with variation in lateral plate size, and three moderate-effect QTL with body size. Together, these findings indicate that genetic underpinnings of skeletal armour variation in Pungitius sticklebacks are more polygenic and heterogenous than those in three-spined sticklebacks, indicating limited genetic parallelism underlying armour trait evolution in the family Gasterostidae.

evolutionary biology↗