Biology subjects

Sakamoto, T.

Publications and source records attributed to Sakamoto, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Integrated transcriptomic and epigenomic profiling of human cartilage reveals coordinated changes in fibronectin expression, splicing, and receptor signaling during osteoarthritis progression

Osteoarthritis (OA) is defined by progressive loss of articular cartilage, but how chondrocytes change as the disease advances is unclear because most studies have focused on end-stage tissue. We profiled human knee articular cartilage across the full range of macroscopic OA grade, from young healthy to aged severe OA donors, by bulk RNA sequencing of 92 knees, single-nucleus RNA sequencing of 108,600 chondrocyte nuclei from 30 donors and single-nucleus multiome sequencing of 24 of these donors, treating grade as a continuous variable. With increasing grade, cartilage increased extracellular matrix (ECM) synthesis and remodeling genes, lost glucocorticoid-responsive, lipid-metabolic and antioxidant programs, and changed the splicing of a small set of ECM transcripts, led by the extra domain B (EDB) exon of fibronectin (FN1). Nine chondrocyte clusters were present in every disease stage and formed a continuum ordered by cartilage zone and hypertrophic differentiation, with PRG4+ superficial and COL10A1+ hypertrophic chondrocytes as the only distinct cell types at its ends and a pre-hypertrophic state between them. With grade, all clusters shared a response in which ECM production rose and homeostatic programs fell, and they differed in which of its components was strongest: ECM production in the superficial cells, the secretory pathway in the hypertrophic and CYTL1+ cells, and inflammatory signaling in the ANXA1+ and CRISPLD2+ cells. Inferred communication between chondrocytes was remodeled with stage. FN1 was induced in every cluster in excess of its fibril-assembly machinery, together with the fibronectin-cleaving protease HTRA1, and FN1 signaling shifted in receptor use from integrin 5{beta}1 toward CD44 and, less robustly, v{beta}8, accompanied by a rise in TGF-{beta}/SMAD response genes. In four early-OA donors, tenascin-C was already largely induced and the FN1 receptor shift from 5{beta}1 toward CD44 was partly present, whereas the rise of FN1 outside superficial chondrocytes, of FGF1 and of developmental and ossification programs came with progression. Chromatin accessibility changed in the same direction across clusters, with regions linked to FN1 opening and regions linked to ITGA5 closing. OA progression in human cartilage therefore appears to be a change of chondrocyte state that differs in emphasis along a zonal and hypertrophic continuum and includes changes in fibronectin regulation, production, processing, and receptor engagement.

bioinformatics↗

bioRxiv2026

Method-dependent biases in cell type detection between single-cell and single-nucleus RNA sequencing in the photosymbiotic acoel Praesagittifera naikaiensis

Background Comparisons of single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq) data have been described in some mammalian tissues and, subsequently, in Drosophila, but remain unexplored in most invertebrate lineages. The xenacoelomorphs occupy key phylogenetic positions, yet they differ anatomically from mammals. They have a reduced extracellular matrix, high-salt body fluid, and no circulatory system. Despite these differences, they possess a well-developed nervous system. One of the xenacoelomorphs, the photosymbiotic acoel (Praesagittifera naikaiensis) also harbours symbiotic Tetraselmis algae, whose RNA can be co-captured with host RNA. Results We compared scRNA-seq and snRNA-seq data from whole P. naikaiensis specimens. Both methods yielded high-quality data with comparable gene detection but a larger share of scRNA-seq reads derived from symbiotic algae. Gene-level analyses revealed that neural genes were enriched in snRNA-seq relative to non-neural genes. Cross-method label transfer and integration-based validation identified six snRNA-seq clusters, including some neural populations, that lacked a clear scRNA-seq counterpart. In contrast, three cell populations, including muscle and metabolically active clusters, were reciprocally validated as captured by both methods. Conclusions Our results show that key snRNA-seq advantages, particularly the enhanced recovery of neural transcripts, are recapitulated in our dataset, which is consistent with previous reports in mammals. Furthermore, snRNA-seq reduces symbiont-derived reads and recovers several cell populations underrepresented in scRNA-seq. These findings provide practical guidance for cell atlas construction in non-model, symbiotic invertebrates.

genomics↗

bioRxiv2026

Mitigating biases of rescaling in forward-in-time population genetic simulations

Forward-in-time population genetic simulations are widely used in evolutionary analyses, but simulating large populations and long genomic regions remains computationally demanding. To reduce this cost, parameter rescaling is widely employed, in which the original evolutionary process is approximated by one with a smaller population size and fewer generations. Recently, several studies using the SLiM simulator have raised concerns about the accuracy of this rescaling approach. In this study, we show that many of the biases reported in these studies can be mitigated by using a different simulation algorithm. These results reveal that the accuracy of parameter rescaling depends on how well the simulation algorithm preserves diffusion-limit properties under rescaling.

genetics↗

bioRxiv2026

A simulation-based method for genotype-environment association analysis

Genotype-environment association (GEA) analyses are widely used to identify loci underlying local adaptation by examining correlations between allele frequencies and environmental variables across a species' range. A major challenge for this approach is distinguishing true adaptive signals from spurious associations arising from population structure. Several methods have been developed to account for population structure, but these methods can suffer from reduced statistical power or increased false positives under some conditions. To address this, we introduce a new GEA method, termed SimGEA. In essence, SimGEA infers a neutral evolutionary model that reproduces the population structure observed in empirical data and uses this model to simulate neutral alleles. By applying the same GEA statistic to both the empirical and simulated data, SimGEA evaluates the significance of observed associations against neutral expectations that account for population structure. We compared the performance of SimGEA with that of existing GEA methods, including LFMM2 and BayPass, using simulations of local adaptation in two-dimensional space. We found that SimGEA consistently controlled the false discovery rate without substantially sacrificing statistical power across the scenarios examined. These results suggest that calibrating statistics using neutral simulations provides a robust and flexible approach for accounting for population structure in GEA analyses.

genetics↗

bioRxiv2026

Expanding the Frontiers of Structural Analysis in Short RNAs by Ultra-High Field 1.3 GHz NMR

Residual dipolar couplings (RDCs) obtained via magnetic field-induced alignment offer a powerful, media-free approach for the structural analysis of biomolecules. However, their detection in short, fast-tumbling nucleic acids remains elusive at conventional magnetic fields due to insufficient alignment and sensitivity. Here, we demonstrate the direct observation of these RDCs at 1.3 GHz in a 14-mer hairpin fragment derived from an HIV-1 Vif-targeting aptamer. The 1JNH scalar couplings of imino protons were measured at fields ranging from 600 MHz to 1.3 GHz. While the coupling constants remained invariant between 600 and 900 MHz, a clear deviation was exclusively captured at 1.3 GHz for all base-paired stem residues, demonstrating the first media-free detection of field-induced RDCs in a short RNA of this size. This breakthrough arises from a synergistic B07/2 scaling, combining enhanced alignment ({propto} B02) and sensitivity ({propto} B03/2). These RDCs showed excellent agreement with the NOE-derived structure. Additionally, the flexible loop residue G8 exhibited no detectable RDC, but displayed a field-dependent TROSY/anti-TROSY intensity inversion at 1.3 GHz, reflecting an unusual 1H chemical shift anisotropy (CSA) tensor that corroborates the local base-packing environment. Our findings highlight 1.3 GHz NMR as an indispensable tool for the structural analysis of short RNAs.

biophysics↗

bioRxiv2026

Pyramiding panicle-level heat avoidance and grain-level heat tolerance improves rice grain appearance under high-temperature grain filling

High temperature during grain filling increases rice grain chalkiness and deteriorates grain appearance under climate warming. Although several loci that reduce chalkiness have been identified, breeding strategies that integrate grain level heat tolerance with panicle level heat avoidance remain limited. Here we characterized SL2033, a chromosome segment substitution line carrying a long IR64 derived segment on chromosome 10, and evaluated the combination of the chromosome 10 segment with Appearance quality of brown rice 1 (Apq1), a quantitative trait locus associated with reduced heat induced chalkiness that acts at the grain level. Compared with its recurrent parent Koshihikari, SL2033 had longer flag leaves, altered vertical plant architecture, and lower panicle temperature. Total starch and protein contents were comparable between the two genotypes, whereas RNAseq analysis of the developing endosperm identified specific differences in heat, stress, and cell wall related transcripts. In a two year field trial, a pyramided line combining the SL2033 derived segment with Apq1 had the highest proportion of perfect grains and lowest frequencies of multiple chalky kernel types during the year with hotter grain filling conditions, with no detectable yield penalty. The pyramided line combined longer flag leaves, as in SL2033, with shorter panicle exsertion, as in an Apq1 near isogenic line, and had the lowest panicle temperature among the tested genotypes. Time series unmanned aerial vehicle imaging also detected genotype dependent differences in plant height during early grain filling, supporting distinct temporal patterns of plant development among the lines. These findings demonstrate that pyramiding genetic loci that confer panicle level and grain level heat tolerance is a promising strategy for improving rice grain appearance under high temperature field conditions, which are becoming increasingly prevalent.

plant biology↗

bioRxiv2026

Rice Cultivars Carrying the Semi Dwarfing Allele Enables High Yield without Lodging under Hairy Vetch based Green Manure

Green manure is a promising strategy for reducing dependence on chemical fertilizers in crop production. However, vigorous growth due to green manure often leads to high yield accompanied by lodging in rice, hindering its practical use in rice cultivation. Here, we show that rice cultivars carrying a semi-dwarfing sd1/ga20ox2 allele achieve high grain yield without lodging under hairy vetch-based green manure conditions. The leading Japanese cultivar Koshihikari exhibited enhanced vegetative growth, increased panicle number, and consequently higher grain yield and quality under green manure conditions in 2023 and 2024 compared with chemical fertilizer management, although this was accompanied by increased culm length and widespread lodging. Among the four GA20-oxidase genes, green manure significantly upregulated Sd1/GA20ox2 mRNA levels. A temperate japonica cultivar, Nijinokirameki, and an indica cultivar, Hokuriku-193, carrying a non-functional sd1/ga20ox2 allele exhibited no lodging under hairy vetch-based green manure management while achieving improved yield performance. Notably, yields obtained under our hairy vetch-based cultivation system were comparable to or exceeded a recently reported high-yield benchmark observed for Hokuriku-193 under chemical fertilizer management in the same region of Japan. These findings suggest that cultivars harboring non-functional sd1/ga20ox2 alleles enable the practical implementation of annual hairy-vetch-rice rotation for sustainable rice production.

plant biology↗

bioRxiv2026

Identification of a microRNA with a mutation in the loop structure in the silkworm Bombyx mori

MicroRNAs (miRNAs) play essential roles in the posttranscriptional regulation of gene expression in organisms. In the process of synthesizing mature miRNAs from miRNA precursors, the miRNA precursors are cleaved via Dicer at their loop structure, after which the miRNA precursors become mature and regulate transcription. However, the consequences of altering the loop sequence are not fully understood. The silkworm Bombyx mori is a lepidopteran insect with many genetic strains. We identified a mutant of the miRNA miR-3260 whose the part of the loop structure was lacking in a silkworm strain with translucent larval skin. Here, we aimed to analyze the role of wild-type miR-3260 and the influence of the mutation of the loop structure in B. mori. First, we identified the genomic region responsible for the translucent larval skin phenotype and determined that the mutated miR-3260 nucleotide sequences. Then, we predicted the binding partners of wild-type miR-3260 using the RNA hybrid tool and found two juvenile hormone (JH)-related genes as targets of wild-type miR-3260. Next, we assessed the relationships between miR-3260 and JH and found that miR-3260 was highly expressed in the Corpora allata and its expression responded to JH treatment. Meanwhile, miR-3260 mimic and inhibitor did not induce the typical phenotypes associated with JH in B. mori. Then, we compared the dicing products from wild-type and mutant miR-3260 precursors and observed that neither form underwent Dicer-mediated cleavage when the loop structure was altered. These results suggest that loop mutations in the miR-3260 precursor may not influence dicing activity, consistent with the lack of observable phenotypic effects.

molecular biology↗

bioRxiv2026

TET2-mutant clonal hematopoiesis prevents T-cell exhaustion and suppresses cancer metastasis

Clonal hematopoiesis (CH) is widely regarded as a risk factor for age-associated disease, yet its influence on solid tumor progression remains poorly understood. Here, we uncover an unexpected tumor-suppressive role for TET2-mutant CH in solid tumors. Through an analysis of over 16,000 cancer patients, we demonstrate that TET2 mutations are associated with a significant reduction in metastatic burden. Mechanistically, we show that Tet2 deficiency prevents terminal exhaustion in CD8+ tumor-infiltrating lymphocytes (CD8+ TILs). This resistance is driven by DNA hypermethylation at regulatory elements of the transcription factor Tox, which prevents the induction of the terminal exhaustion program. Consequently, Tet2-deficient CD8+ TILs maintain stem-like, effector-competent states that mediate durable anti-tumor immunity and suppress metastatic outgrowth. Our findings establish TET2-mutant CH as a natural epigenetic constraint on T-cell exhaustion and uncover a mechanistically defined pathway with translational potential for enhancing anti-tumor immune responses.

immunology↗

bioRxiv2026

A Machine Learning Framework for Serogroup Classification of pathogenic species of Leptospira Based on rfb Locus Profiles

Leptospira is a highly diverse genus traditionally classified by serological assays into more than 30 serogroups and over 300 serovars. However, this classification system is often complex and inconsistent, as cross-reactions between antigens can lead to ambiguous results. Moreover, serological tests such as MAT and CAAT are labor-intensive, require live cultures, and are difficult to standardize across laboratories. To overcome these limitations, we compiled genomic data from 721 pathogenic Leptospira samples obtained from NCBI RefSeq and BIGSdb (Institut Pasteur) to develop a machine learning framework capable of predicting serological classification directly from genomic information. Our approach focuses on the rfb locus, a genomic region associated with lipopolysaccharide biosynthesis and antigenic diversity, and was designed to operate in two stages: the first stage assigns samples to one of four major serological classes, while the second stage classifies them into their respective serogroups. Models from both classification stages achieved high predictive performance, with perfect score in the first and a mean F1-score of 0.948 in the second stage. Feature importance analysis revealed non-random clustering of highly informative genes within the rfb locus and demonstrated that serogroup discrimination is driven by combinatorial patterns of gene presence and absence. Based on the strong genetic coherence observed at the rfb locus and shared antigenic features, we propose the term "seroclass" to designate these higher-order groupings. This approach provides a scalable and reproducible alternative to traditional serological testing and offers valuable applications for epidemiological surveillance, outbreak investigation, and vaccine development within the Leptospira genus. HighlightsO_LIGenomic data enable accurate inference of Leptospira serological classification. C_LIO_LIThe approach predicts serogroups directly from rfb locus gene composition. C_LIO_LIThe model provides a scalable alternative to labor-intensive serological assays. C_LIO_LIWe introduce the term "seroclass", a higher level of serological organization. C_LIO_LIThe proposed framework supports epidemiological surveillance and vaccine design. C_LI

microbiology↗

bioRxiv2026

NAD boosting mediated by CD38 inhibition drives reversal of a pathological vicious cycle of intracrine activity and inflammation in eyelid meibomian gland dysfunction

Vicious cycles--reciprocal cause-and-effect loops that progressively intensify dysfunction--are implicated in many diseases. Here, we examined whether "intracrine" steroidogenesis, a tissue-local mode of hormone production, participates in a pathological vicious cycle in eyelid meibomian gland dysfunction (MGD), the most common cause of evaporative dry eye disease with incidence increasing with age. We show that loss of meibomian intracrine androgen production triggers inflammatory remodeling of the eyelid tarsal plate. Conversely, inflammation suppresses nicotinamide adenine dinucleotide (NAD)-dependent 3{beta}-hydroxysteroid dehydrogenase activity in the meibomian gland, thereby further weakening intracrine steroidogenesis. Mechanistically, we identified inflammation-associated accumulation of the NAD-degrading enzyme CD38 as a key down-regulator for the NAD-dependent intracrine activity. Accordingly, pharmacological inhibition of CD38 (using 78c) in aged mice, restores meibomian cellular NAD levels, rescues intracrine activity, suppresses inflammatory signatures, and promotes recovery of gland size. Thus, our data suggest that boosting NAD availability not only ameliorates meibomian gland dysfunction but also induces a reciprocal "virtuous" cycle, in which suppression of inflammation and restoration of intracrine activity mutually reinforce each other. These findings constitute a previously unknown example in which the reversal of a pathological vicious cycle into a beneficial virtuous cycle underlies the therapeutic effects of NAD boosting and may help combat age-associated meibomian gland disorder.

pathology↗

bioRxiv2026

Spontaneous Emergence and Turnover of the Sex-Determining Locus

Anisogamy is nearly universal across multicellular organisms, yet how two discrete sexes arise in genomes with many recombining autosomal loci remains unresolved. Classic models show that disruptive selection on gamete size can drive anisogamy, but their single-locus assumptions conflict with empirical evidence that sexual differentiation typically involves numerous autosomal genes whose linkage is continuously broken by recombination. Here we develop an evolutionary model of gene regulatory networks (GRNs) to show that disruptive selection favoring complementary mating phenotypes can spontaneously generate a bistable developmental architecture producing two stable sexual phenotypes, together with a master sex-determining locus that biases development toward one or the other. Once such a bistable GRN evolves, the identity of the master regulator becomes flexible, enabling turnover of sex-determining loci without disrupting sexual differentiation. Our results provide a general mechanism for the origin, robustness, and evolutionary lability of sex-determination systems, linking classical gamete-level selection with the emergence of developmental bistability through the evolution of GRNs.

evolutionary biology↗

bioRxiv2025

Activation of neurogenesis improves amyloid-β pathology and cognitive function through AMP kinase signaling in Alzheimer's disease model mice

Adult hippocampal neurogenesis declines with aging and in neurological disorders, leading to cognitive impairment. We previously demonstrated that a treatment of inducing Plagl2, a zinc finger transcription factor gene, and antagonizing Dyrk1a, a gene associated with Down syndrome, referred to as iPaD, can functionally rejuvenate aged neural stem cells (NSCs), thereby enhancing neurogenesis and improving cognition in aged mice. Here, we found that NSC-specific iPaD treatment effectively activated neurogenesis, reduced amyloid-{beta} deposition, and improved cognitive function in Alzheimers disease model mice. Transcriptomic analysis revealed widespread significant changes in gene expression in the hippocampus following iPaD treatment. The upregulated genes included those associated with the activation of astrocytes and microglia involved in amyloid-{beta} clearance, while the downregulated genes included several that are upregulated in Alzheimers disease patients, but whose roles in disease progression remain unclear. Among the latter genes, knockdown of Prkag2, a gene encoding protein kinase AMP-activated non-catalytic subunit gamma 2, in the hippocampus most effectively enhanced neurogenesis and reduced amyloid-{beta} accumulation. Notably, both iPaD treatment and Prkag2 knockdown activated AMP-activated protein kinase signaling, thereby upregulating genes involved in autophagy and cellular homeostasis. These results suggest that Prkag2 may represent a promising therapeutic target for neurodegenerative diseases, including Alzheimers disease.

neuroscience↗

bioRxiv2025

Dissecting Agronomically Favorable Genotypes in Temperate Japonica Rice via Haplotype Analysis of a Japan-MAGIC Population

O_LICrop breeding assembles genomic variants into cultivars via crossing and selection. Phenotypic selection has improved yield and lodging tolerance but has limited genetic insights. We show how specific genomic variants and their combinations underpin advances in modern rice breeding in Japan. C_LIO_LIThrough genome-wide association study using a multi-parent advanced-generation intercross population derived from four temperate japonica cultivars, we identified 11 quantitative trait loci (QTLs) for key agronomic traits, including days to heading, shoot biomass, panicle length, and culm length under field conditions. GA20ox1, GA20ox2, and Hd1 were among the QTLs, and their natural variants were well conserved in temperate japonica cultivars bred in Japan, underscoring distinct selection pressures at these loci. C_LIO_LIBy integrating genotype data with 5-year yield-performance-evaluation trials of elite cultivars, we found that cultivars carrying multiple-copy GA20ox1 and functional Hd1, together with non-functional ga20ox2, tended to have shorter culms and higher grain yield than cultivars with multiple-copy GA20ox1, functional Hd1, and GA20ox2. This yield advantage was consistent across latitudes in Japan. C_LIO_LIThese results reveal favorable genotype combinations underlying modern japonica improvement and provide a genomic framework for breeding semi-dwarf, high-yielding cultivars adapted to temperate rice-growing regions in Asia. C_LI

genomics↗

bioRxiv2025

Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cycling

ObjectiveDelineating the nodal control points that maintain whole-body energy homeostasis is critical for understanding potential treatments of obesity and cardiometabolic diseases. The nutrient-sensing transcription factor MondoA is a regulator of skeletal muscle fuel storage, where muscle-specific inhibition improves glucose tolerance and insulin sensitivity. However, the role of MondoA in whole body energy metabolic homeostasis is not understood. MethodsGeneralized MondoA knockout (gKO) mice were generated and assessed for glucose tolerance and insulin sensitivity, body composition, energy expenditure, cold tolerance, and tissue specific transcriptional changes in response to high fat diet. Complementary studies in cultured human adipocytes assessed the impact of MondoA deficiency on substrate utilization and lipolysis. ResultsgKO mice are protected from diet-induced obesity and insulin resistance, through increased whole body energy expenditure. gKO mice exhibit reduced brown and inguinal white adipose tissue mass, without evidence of beiging. The gKO mice are hyperlactatemic and isolated MondoA-deficient adipocytes have increased 2-deoxyglucose uptake and glycolytic function. Lastly, gKO mice and KO adipocytes display increased circulating glycerol relative to free fatty acids in response to adrenergic stimulus consistent with elevated re-esterification. However, this phenotype is not recapitulated in adipocyte-specific KO mice. ConclusionsMondoA deficiency alters cellular sensing of nutrient availability and storage/utilization mechanisms. In the whole-body setting, this results in increased energy expenditure, potentially related to increased glucose uptake and glycolytic flux driving glycerol synthesis to supply high rates of lipolysis and lipid re-esterification. These results suggest that MondoA functions to maintain fuel storage and when lost, inter-organ futile cycling ensues. O_FIG O_LINKSMALLFIG WIDTH=140 HEIGHT=200 SRC="FIGDIR/small/680559v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1ccf42dorg.highwire.dtl.DTLVardef@b2da28org.highwire.dtl.DTLVardef@1081aforg.highwire.dtl.DTLVardef@1b2168d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO 1) Global MondoA deficiency drives 2) tissue glucose uptake which in skeletal muscle is 3) converted and excreted as lactate, while in adipose tissue 4) triglyceride re-esterification requires 5) de novo glycerol synthesis to feed into the futile cycle. C_FIG

physiology↗

bioRxiv2025

Protein Dimension DB: A Unified Protein Repository for Representation Learning and Functional Analysis

Inspired by the success of large language models in areas like natural language processing, researchers have applied similar architectures, notably the Transformer, to protein sequences. Thanks to these developments, Protein Language Models (PLMs) have become important resources for diverse tasks such as predicting protein family, function, solubility, cellular location, molecular interactions and remote homology. However, the size of the best performing PLMs (which can be up to 15B parameters) requires substantial computational power. Protein Dimension DB addresses this critical bottleneck by providing a centralized, version-controlled resource of precomputed protein embeddings, experimentally validated molecular function annotations, and taxonomic encodings. The database integrates embeddings from seven state-of-the-art PLMs, including ProtT5, ESM2, and Ankh variants for all Swiss-Prot/ UniProt proteins. These models were compared by benchmarking molecular function prediction. Tests revealed that hybrid embeddings (e.g., Ankh Base + ProtT5) outperformed single-model approaches with minimal dimensionality increases. Taxonomic encodings further boosted performance by 2.9% AUPRC, demonstrating lineage-aware learning. By providing embeddings in Parquet format -- a columnar storage optimized for machine learning workflows -- the resource eliminates GPUdependent preprocessing and reduces storage requirements. This enables immediate use in resource-constrained environments while maintaining backward compatibility through versioned releases. All datasets are freely accessible via Github and HuggingFace, with unified metadata enabling applications from functional annotation to evolutionary studies. Protein Dimension DB bridges the gap between cutting-edge PLMs and practical biological research, offering researchers standardized inputs for reproducible, multi-modal protein analysis.

bioinformatics↗

bioRxiv2025

Tracing genome size dynamics in sharks and rays with inclusive sequence analysis by the Squalomix Consortium

Genomes have maintained stable sets of protein-coding genes during evolution, while chromosome organization and genome size vary drastically. Changes in genome size are often attributed to variable amounts of repetitive sequences, including transposable elements. However, it remains poorly understood how such changes were accommodated while maintaining other genomic components. Elasmobranchs, including sharks, rays, and skates, exhibit high among-species variation of genome size and high within-species variation of chromosome length, offering a unique study system to address the question. In this study, we present the first whole genome sequences of the whitebelly skate with remarkably small genome size among elasmobranchs (2.2 Gb), and the red stingray. These chromosome-scale assemblies enabled the assessment of genomic compositions including centromeres and non-coding elements, which revealed notable profiles of tRNA loci and unbiased intragenomic distribution of transposons in elasmobranch genomes. Comparative analyses across these species revealed a shared genomic architecture characterized by correlations of intergenic and intronic sequence lengths with chromosome sizes, with repetitive element accumulation in elongated regions. We analyzed tandemly duplicated genes with high copy number variability. This genome-wide survey revealed the tendency for more frequent tandem gene duplications along with genome size expansion. We document the batoid HoxC cluster in the red stingray genome, which has undergone extensive repetitive element invasion and co-localizes with the HoxB cluster on a sex chromosome. Our study demonstrates an inclusive analysis encompassing both coding and non-coding regions, adaptable to more species in the taxon and a basis for molecular-level understanding on phenotypic diversity of elasmobranchs.

genomics↗

bioRxiv2025

Maintenance of polymorphism in spatially heterogeneous environments

Local adaptation occurs when species adapt to spatially heterogeneous environments. The stability of local adaptation is determined by selection-migration-drift balance: selection favours adaptive divergence whereas migration and random genetic drift cause the collapse of the divergence. How this balance determines the dynamics of local adaptation has been extensively studied. However, owing to the complexity of multi-population models, most previous theories used models with simple population structure and environmental variation, limiting their applicability to complex situations in nature. To address this issue, we developed a new theoretical method to analyze complex multi-population models, allowing heterogeneity in selection, migration, and population density. In essence, our method approximates a spatial model by a panmictic one-population model while retaining the core stochastic structure, enabling the application of conventional diffusion methods. By comparing with simulations, we confirmed that our method accurately describes stochastic evolutionary dynamics in various spatial models, provided sufficient levels of migration. This method is then applied to examine the effect of environmental distribution in 2D space. Assuming landscapes with different levels of the spatial autocorrelation of the environment, we found that the maintenance of locally adaptive alleles is significantly promoted when the spatial autocorrelation is high. These results highlight how complex spatial heterogeneity, as seen in nature, could affect the qualitative outcome of evolution.

genetics↗