Biology subjects

Xu, Z.

Publications and source records attributed to Xu, Z..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Targeting Circulating FABP4 Ameliorates Obesity-Associated Hepatic Steatosis

Obesity is a major driver of hepatic steatosis, yet the molecular link between excess adiposity and hepatocellular lipid accumulation remains incompletely defined. Here, we identify circulating fatty acid-binding protein 4 (FABP4) as a key mediator of adipocyte-hepatocyte lipid crosstalk in obesity. Analyses of human liver specimens and mouse models reveal aberrant accumulation of FABP4 protein--but not transcript--in hepatocytes during steatosis, indicating an extrinsic source. Genetic deletion of FABP4, specifically in adipocytes, protects against high fat diet-induced hepatic steatosis without altering obesity or systemic lipid levels. Mechanistically, circulating FABP4 directly binds to hepatocytes, facilitating free fatty acid uptake. Furthermore, we developed a high-affinity humanized monoclonal antibody that selectively neutralizes circulating FABP4, blocks hepatocyte binding, suppresses fatty acid uptake, and markedly attenuates hepatic steatosis in multiple obese mouse models. These findings establish circulating FABP4 as a pathogenic lipid chaperone and a promising therapeutic target for obesity-associated hepatic steatosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/701451v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@5b91d5org.highwire.dtl.DTLVardef@1c34892org.highwire.dtl.DTLVardef@1d17ea9org.highwire.dtl.DTLVardef@d2b43c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHepatocytic accumulation of extrinsic FABP4 links adiposity to liver lipid deposition. C_LIO_LISpecific deletion of FABP4 in adipocytes prevents hepatic steatosis without affecting systemic lipid levels or obesity. C_LIO_LICirculating FABP4 derived from adipocytes directly binds hepatocytes to facilitate free fatty acid transfer. C_LIO_LIBlocking circulating FABP4 with a high-affinity anti-FABP4 monoclonal antibody inhibits hepatocyte lipid uptake and attenuates steatosis in multiple obese mouse models. C_LI

pathology↗

bioRxiv2026

Full-length transcriptome atlas of Panax vietnamensis var. fuscidiscus reveals novel genes and alternative splicing in tissue-specific biosynthesis of ocotillol-type saponins

BackgroundPanax vietnamensis var. fuscidiscus is the only known Panax species that accumulates exceptionally high levels of ocotillol (OCT)-type ginsenosides, particularly majonoside R2. However, the molecular mechanisms underlying OCT-type ginsenoside biosynthesis remain largely uncharacterized, due in part to the absence of comprehensive full-length transcriptome data and complete gene annotations. ResultsWe combined PacBio single-molecule real-time (SMRT) and Illumina RNA sequencing (RNA-Seq) technologies to construct the first tissue-specific, full-length transcriptome atlas of P. vietnamensis var. fuscidiscus. A total of 281,468 non-redundant transcripts were assembled, including 8,089 novel genes not present in existing annotations, substantially expanding the documented gene repertoire of this species. We identified 21 candidate genes putatively involved in triterpenoid saponin biosynthesis and uncovered distinct tissue-specific expression patterns across the oleanane (OA)-, protopanaxadiol (PPD)-, protopanaxatriol (PPT)-, and OCT-type biosynthetic pathways. Notably, we detected 46,917 alternative splicing (AS) events, with over 45% of expressed genes producing multiple isoforms. Several key biosynthetic genes--including dammarenediol synthase (DDS), cytochrome P450 716A53v2 (CYP716A53v2), and mevalonate diphosphate decarboxylase (MVD)--exhibited tissue-specific splicing patterns, such as retained introns and exon skipping, which may contribute to functional diversification of isoforms involved in OCT-type ginsenoside biosynthesis. These results highlight the importance of post-transcriptional regulation and transcript diversity in the evolution and fine-tuning of specialized metabolic pathways. ConclusionsThis study establishes a high-quality, full-length transcriptomic resource for P. vietnamensis var. fuscidiscus, revealing previously undescribed genes and extensive alternative splicing events related to ginsenoside biosynthesis. Our findings provide novel molecular insights into the mechanisms regulating OCT-type saponin accumulation and offer a foundation for future research into the functional characterization, regulatory mechanisms, and synthetic biological production of rare triterpenoid saponins.

plant biology↗

bioRxiv2026

Single-Cell Multi-Omics Insights into BMI-Mediated Immune-Related Disease Risk

This study is based on the Chinese Immune Multi-Omics Atlas (CIMA) cohort and performs an integrated single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from 210 individuals aged 20-29, comprising 3,311,699 scRNA-seq cells and 1,839,860 scATAC-seq cells, to decipher immune characteristics across different body mass index (BMI) categories. By integrating gene regulatory network (GRN) and cell type-level molecular quantitative trait loci (xQTL) data, and conducting summary-data-based Mendelian randomization (SMR) analysis in conjunction with genome-wide association studies (GWAS) of BMI-mediated immune-related diseases, we identified key disease-associated cell types and molecular features. Using rheumatoid arthritis (RA) as an example, multi-omics evidence revealed that in MAIT-SLC4A10 cells of underweight individuals, increased chromatin accessibility at the CCR6 locus (chr6:167119627-167120128) and enhanced transcriptional activity of RORC/RORA collectively drive elevated CCR6 expression, which may represent a potential molecular mechanism underlying the higher risk of RA in underweight populations. Our study leverages single-cell multi-omics data to systematically dissect the molecular mechanisms by which different BMI categories mediate susceptibility to immune-related diseases through coordinated regulation of immune cell chromatin accessibility, transcription factor activity, and downstream gene expression.

bioinformatics↗

bioRxiv2026

Dual Inhibition of MYRF Cleavage by Its JM Region and PAN-1 CCT Gates Developmental Timing in C. elegans

Post-embryonic development proceeds through discrete stages, yet the mechanisms that coordinate transitions between stages remain incompletely defined. The transmembrane transcription factor MYRF undergoes intramolecular cleavage to release a nuclear-localized fragment essential for developmental progression in C. elegans. Previously, we showed that PAN-1 as a key partner required for MYRF activity during development. PAN-1 promotes MYRF trafficking to the cell membrane--an essential step for MYRF cleavage--through interactions between their extracellular domains (Xia et al., 2021). Here, we show that MYRF-1 cleavage and nuclear translocation oscillate with larval stage transitions in C. elegans, peaking mid-to-late stage and being suppressed during molts. Using endogenous gene editing and mutant reporters, we identify an uncharacterized juxtamembrane (JM) region in MYRF-1 that self-inhibits cleavage. JM deletion triggers premature MYRF-1 nuclear entry, early lin-4 activation, growth defects, and adult lethality. We further demonstrate that the cytoplasmic tail (CCT) of the transmembrane protein PAN-1 acts as a predominant trans-inhibitor of MYRF-1 cleavage, coupling extracellular association with cytoplasmic inhibition. PAN-1 CCT deletion causes near-constitutive MYRF-1 nuclear accumulation, leading to premature lin-4 activation, accelerated M-cell division, and larval lethality. Removing these inhibitory mechanisms on MYRF-1 cleavage overrides nutrient-responsive developmental checkpoints. These findings uncover dual inhibitory mechanisms governing MYRF-1 cleavage and establish MYRF-1 cleavage as a key gatekeeper of developmental timing.

developmental biology↗

bioRxiv2026

Asymmetric Division in a Two-Cell-Like State Rejuvenates Embryonic Stem Cells

A fundamental question in biology is whether cellular aging is inevitable. Embryonic stem cells (ESCs) challenge this paradigm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow fates of single ESCs, we show here that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo asymmetric divisions, segregating accumulated DNA damage into one daughter lineage destined for elimination, while producing a second lineage that reverts to the pluripotent state. Importantly, the latter lineage exhibits signs of rejuvenation, including reduced DNA damage and enhanced chimeric efficiency. These findings underscore the crucial role of asymmetric cell division in maintaining the long-term health of the ESC lineage against mounting damage within individual cells, a potential model for studying cellular aging and rejuvenation in mammalian cells.

cell biology↗

bioRxiv2025

MicroGenomer: A Foundation Model for Transferable Microbial Genome Representations Enabling Multi-scale Genomic Understanding and Ecophysiological Trait Prediction

Microorganisms underpin global biogeochemical cycles and represent a vast, underexplored reservoir for sustainable biotechnology and human health. Their diversity, arising from the interplay of numerous genes within holistic genomic contexts, dictates complex ecophysiological traits across varied environments. To bridge the gap between complex genomic sequences and associated biological functions and phenotypic outcomes, we present MicroGenomer, a foundation model for transferable microbial genome representations enabling multi-scale genomic understanding and ecophysiological trait prediction. MicroGenomer leverages a hierarchical training strategy comprising pre-training on large-scale genomic sequences (234.5 billion base pairs), domain-specific mid-training using the GTDB-curated marker gene set, and task-specific post-training. Despite a streamlined architecture of 470 million parameters, MicroGenomer achieves performance on key tasks competitive with models nearly 85 times its size. Advancing beyond established gene-scale encoders, MicroGenomer generates robust embeddings at the genome scale for downstream modeling. Extensive evaluations demonstrate that MicroGenomer effectively captures phylogenetic structures in species space, excelling in geneand genome-scale understanding as well as ecophysiological trait prediction. The practical utility of these capabilities is further demonstrated by targeted wet-lab validation on newly isolated strains, indicating that MicroGenomers predictions provide reliable guidance for biological experiments. Collectively, MicroGenomer offers a high-performance, resource-efficient framework that transforms raw sequence data into actionable biological insights, providing a powerful foundation for microbiome research and biotechnology.

bioinformatics↗

bioRxiv2025

Improved surfactant-assisted one-pot sample preparation for robust convenient single cell proteomics

Recent advances in mass spectrometry-based single-cell proteomics (SCP) technologies have revolutionized the SCP field for comprehensive characterization of cellular heterogeneity. However, most of the current SCP approaches employ sub-{micro}L to 1 {micro}L processing volume for effective single-cell sample preparation using either ultralow-volume specialized devices or a 384-well plate by frequently adding water to the plate well to compensate water evaporation, which greatly limits their broad accessibility and analytical robustness. Here we report a robust convenient SCP method termed iSOP (improved Surfactant-assisted One-Pot processing) for processing of single cells at the low {micro}L processing volume using the 384-well plate with tight sealing to avoid sample drying loss. This iSOP SCP method was built upon our previously developed SOP method by the replacement of a PCR tube or 96-well plate with the low-volume 384-well plate and systematic optimization of the single-cell processing conditions. After optimization, 3 {micro}L was selected as the processing volume with a mixture of 2 ng trypsin and 2 ng Lys-C enzymes in terms of robustness, detection sensitivity, and operation convenience. With a commonly accessible LC-MS platform, iSOP-MS can detect and quantify [~]1,200-1,800 protein groups from single HeLa or MCF7 cells. Application of iSOP-MS to two neuroblastoma cell lines has demonstrated that iSOP-MS enabled reliable identification of an average of [~]1,700 and [~]2,050 protein groups from single BE2-C and SK-N-SH cells, respectively, and precise characterization of cellular heterogeneity between the two distinct cell types and within the same cell type. When compared to other available SCP methods, iSOP-MS is more robust and convenient for routine, cost-effective quantitative SCP analysis.

biochemistry↗

bioRxiv2025

A changing hierarchy of environmental time cues guide development of the migratory pest moth Loxostege sticticalis

Insects use environmental cycling cues to align developmental progression. In holometabolous insects, the progression from larva to adulthood entails decision points, i.e., larval diapause and adult eclosion, that engage circadian timing mechanisms. What environmental time cues dynamically interact to regulate these developmental checkpoints lying at the intersection of the orthogonal timing systems, remains elusive. We used the seasonally migratory insect Loxostege sticticalis to disentangle the influence of photoperiod regimes and temperature conditions at distinct checkpoints of larval growth and metamorphosis. We here employed sensory conflict paradigms to reveal that the relative dominance of these cues changes over ontogeny. Our results confirm that diapause is induced primarily by the photoperiod during early larval development, rather than by the diel thermoperiod. In contrast, the circadian clock-controlled adult eclosion, normally locked to the first hour of the daybreak, is jointly controlled by light and temperature cycles. An increase in the constant temperature advanced the peak timing of daily eclosion. On the other hand, the interval timing mechanism regulating the duration of the eclosion event is tuned specifically by the night temperatures. Together, photoperiod dominates early developmental decisions, but thermoperiod gains weight at later stages. This shifting hierarchy provides a mechanistic framework for understanding phenological plasticity. Since the timing of eclosion presents a window of increased vulnerability for this pest insect, our results could help to optimize the daily timing of pest management intervention under variable thermal and light conditions.

ecology↗

bioRxiv2025

Flu Virus Infection in Juvenile Mice Leads to Lifelong Multi-Organ Damage and Parkinsonian Pathological Changes in Aging

The widespread prevalence of Long COVID underscores the potential for viral infections to exert prolonged effects on hosts long after initial recovery. Despite this recognition, the long-term and even lifelong consequences of viral infections remain poorly understood. In this study, we infected juvenile mice with influenza viruses and systematically examined the lifelong effects (from 4 to 450 days post-infection) of these infections. Pathological analysis revealed persistent lifelong damage in multiple organs, including chronic lung inflammation and fibrosis, along with significant cardiac and renal pathology. Viral infection led to substantial neuronal loss in key brain regions of mice (hippocampal CA1, CA3, and striatum) during middle and old age. Strikingly, we identified two hallmark pathological features of Parkinsons disease - dopaminergic neuron degeneration and Lewy body-like -synuclein inclusions - in middle and aged infected mice. Transcriptomic profiling demonstrated sustained upregulation of inflammation-related genes in both lung and blood tissues, correlating with observed pathological changes. Lung-derived secreted proteins, encoded by differentially expressed genes, may mediate cross-organ communication affecting cardiac, renal, and neurological function. Brain transcriptome analysis at three months post-infection revealed downregulation of neurodevelopmental genes, potentially contributing to subsequent neuronal loss and Parkinsonian pathology. These findings collectively suggest that pulmonary influenza infection can induce systemic multi-organ effects through both secretory pathways and chronic inflammatory responses. The study offers crucial insights for developing more effective strategies to prevent and manage infectious diseases and their long-term sequelae.

microbiology↗

bioRxiv2025

Ser129 Phosphorylation Paradox: Non-phosphorylated α-Synuclein Drives Parkinson' s Disease-like Pathogenesis in Vivo

Accumulation of phosphorylated -synuclein at serine 129 is a hallmark of Parkinsons disease (PD), but its pathogenic role remains controversial. We conducted longitudinal studies using non-phosphorylatable S129A and phosphomimetic S129D -synuclein global knock-in mice. Unexpectedly, the S129A mice--rather than S129D mice--developed reproducible olfactory, motor, and cognitive deficits, dopaminergic dysfunction and neurodegeneration, -synuclein insolubility, and Lewy-like inclusions by 3 to 9 months, with progressive worsening up to 12 months of age. Spatial transcriptomics and electron microscopy revealed mitochondrial, synaptic, and protein ubiquitination abnormalities in the substantia nigra of S129A -synuclein mice. Viral vector-mediated nigral overexpression of S129D--synuclein or systemic administration of an anti--synuclein-aggregation drug partially alleviated the early neurological phenotypes of S129A mice. These results implicate non-phosphorylatable -synuclein as a direct pathogenic driver for PD.

neuroscience↗

bioRxiv2025

Neocortical temporal patterning by a two-layered regulatory network

In the developing neocortex, a diverse array of neurons with defined types and abundances are systematically generated by a limited population of radial glial progenitors (RGPs) as they undergo successive fate changes. The molecular regulation behind this intricate temporal patterning remains elusive. We undertook in-depth single-cell multi-omics analyses, discovering a two-layered regulatory framework at the core of this process. Central to this are global temporal regulators positioned above a temporal network, consisting of series of transcriptional factor (TF) hub groups under sequential state transitions. This temporal network operates not by restricting TF expressions to discrete temporal windows, but through coordinated transcriptional and chromatin-accessibility dynamics that modulate transient TF regulatory activity. Moreover, global temporal regulators specify the duration of each cascading stage and, consequently, the number of progenies generated at each stage. Loss of global temporal regulators protracts RGP lineage progression, whereas their increased activity accelerates it. These findings suggest a two-layer temporal regulatory system controlling RGP lineage progression and neural progeny output duality in mammalian neocortical development.

neuroscience↗

bioRxiv2025

Centromeres and pericentromeric heterochromatin are accessible in living Schizosaccharomyces pombe cells

Chromatin is intrinsically repressive, limiting access to DNA, implying a major regulatory role. Studies with nuclei support this model. However, we have shown previously that genomic DNA is completely accessible in living budding yeast and human cells, except for centromeric chromatin. The fission yeast, Schizosaccharomyces pombe, provides a tractable model for heterochromatin. As in mammalian cells, S. pombe heterochromatin is marked by histone H3K9 di- and tri-methylation (H3K9me2/3), introduced by the Clr4 histone methylase, and heterochromatin protein 1 (HP1/Swi6). Here, we developed a copper-inducible DNA methyltransferase system to measure heterochromatin accessibility in living S. pombe cells. We find that euchromatin and heterochromatin are similarly and generally accessible in vivo, indicating that S. pombe chromatin is globally dynamic. S. pombe centromeres are also fully accessible, unlike budding yeast and human centromeres. In contrast to living cells, S. pombe chromatin is mostly inaccessible in isolated nuclei, primarily due to tight nucleosome spacing with very little linker DNA. Loss of Clr4 or Swi6 has little effect on genome accessibility in live cells or nuclei, suggesting that the S. pombe H3K9me/HP1 system does not repress transcription by preventing access to DNA.

genomics↗

bioRxiv2025

Steric Gating Dictates Selective Activation of BIRC6 by UBA6 Over UBA1

The giant E2-E3 chimera BIRC6 is specifically activated by the ubiquitin-activating enzyme UBA6, but not by UBA1. This specificity allows BIRC6 to ubiquitinate downstream substrates (e.g., caspases) and thereby regulate apoptosis. However, the molecular mechanism that underlies UBA6mediated specific activation of BIRC6 remains elusive. Here, we used a UbDha (Ub residue 76 dehydroalanine) probe to achieve one-step, activity-based trapping of the transient transthioesterification intermediate, and resolved the cryo-EM structures of two key complexes: 1) the doubly loaded UBA6-BIRC6UBC-UbT-UbA complex (3.4 [A] resolution) and 2) the singly loaded UBA6-BIRC6UBC-UbT complex (3.3 [A] resolution). Structural analysis reveals that the specific BIRC6-UBA6 pairing is dictated by steric compatibility between an insertion loop (residues 4649- 4653) in BIRC6s UBC domain and UBA6s gate helix. Unlike UBA1, UBA6 avoids steric clash with this insertion loop via two key conformational changes: a ~30{degrees} clockwise rotation and a 19 [A] displacement of its gate helix. These conformational changes collectively create a compatible cavity to accommodate the insertion loop. Biochemical validation confirms two key findings: 1) truncating BIRC6s insertion loop rescues UBA1-mediated ubiquitin charging of BIRC6UBC; 2) swapping UBA6s gate helix with that of UBA1 abolishes UBA6s transthioesterification activity towards BIRC6UBC. Our study provides key structural insights into the molecular basis of E1-E2 pairing specificity and advances our mechanistic understanding of apoptotic signalling.

biochemistry↗

bioRxiv2025

Sir proteins impede, but do not prevent, access to silent chromatin in living Saccharomyces cerevisiae

Gene silencing at the mating type loci in budding yeast (HMRa and HML) depends on the Sir proteins. Sir2, Sir3 and Sir4 are indispensable for silencing, whereas Sir1 has a more limited role. The Sir proteins are also involved in repression at telomeres and ribosomal DNA (rDNA) repeats. Proposed mechanisms for Sir-mediated silencing include limiting access to silenced DNA and inhibition of transcript initiation and/or elongation. Using an inducible M.SssI DNA methyltransferase expression system, we showed previously that the silenced mating type loci are methylated at a much slower rate than the rest of the genome in vivo. Here, we show that, in the absence of Sir2, Sir3 or Sir4, the silenced loci and the telomeric X elements are methylated at a similar rate to the rest of the genome, indicating that these Sir proteins impede access, but do not prevent it. The rDNA repeats are methylated faster in the absence of Sir2 and, to a lesser extent, of Sir3, but not of Sir4. The methylation rates of adjacent rDNA repeats are not strongly correlated in wild-type cells, suggesting that Sir proteins silence rDNA repeats randomly. Loss of Sir1 increases the methylation rate at HMRa but not at HML, telomeres or rDNA. Our data indicate that steric occlusion is unlikely to be the primary mechanism of silencing, since silenced DNA is accessible in vivo, albeit at a slower rate than elsewhere in the genome.

genetics↗

bioRxiv2025

Cell State Chaos Underpins the Evolution of SMARCA4-Deficient Dedifferentiated Endometrial Cancer

Dedifferentiated endometrial carcinoma (DDEC) is a histologically unique cancer type, wherein well-differentiated regions lie adjacent to morphologically distinct, high-grade lesions that are histologically undifferentiated. Previous studies have determined that in nearly half of the cases dedifferentiation is associated with the genomic inactivation of SMARCA4, a catalytic subunit belonging to the SWI/SNF chromatin remodelling complex (SWI/SNF CRC), suggesting that SMARCA4 loss causes dedifferentiation. Herein, using gene editing, we reveal that when serially passaged in mice, SMARCA4-deficient endometrial cancer cells repeatably and predictably generate heterogeneous admixtures of differentiated and undifferentiated cells, resembling human DDEC. Surprisingly, despite this metamorphosis, SMARCA4 loss does not induce lineage plasticity nor reprogramming to a less differentiated fate. Rather, single-cell sequencing combined with barcoding demonstrated that SMARCA4 loss induces a dysregulated epigenome that allows cells to randomly move through cellular states that are otherwise shared with SMARCA4-expressing well-differentiated cancer cells. This finding was validated using a cohort of patient samples, such that epithelial fate markers (E-CADHERIN) can be detected in morphologically undifferentiated cells. Collectively, this work constitutes the first repeatable model of human dedifferentiated cancer and suggests that histological dedifferentiation is not due to the acquisition of a stem cell-like fate. Rather, undifferentiated tissue emerges due to epigenomic dysfunction concomitant with the arbitrary movement of cancer cells between cellular states.

cancer biology↗

bioRxiv2025

Plant Face: Machine learning decodes genetic, environmental and developmental imprints in leaf appearance

Leaf appearance is a crucial plant phenotype. However, traditional methods for extracting this information are inefficient, limiting its full utilization. Deep learning based on convolutional neural networks (CNNs) enables us to capture previously inaccessible information from images. In this study, we made the surprising discovery that the leaf appearance of each individual plant is unique. Using deep learning, leaves from one plant could be efficiently distinguished from those of another plant of the same species and cultivar. We term this phenomenon the "Plant Face" and suggest the potential to develop a "plant face recognition system," analogous to human facial recognition. We also applied similar methods to study the relationship between leaflet appearance and their position on compound leaves, leaf bilateral symmetry, and differences in leaves from twining stems with different chirality. These results collectively indicate that plant genetic characteristics, growth conditions, and developmental features can be stored within their appearance. With appropriate decoding, leaf appearance is poised to play an increasingly important role in phenomics. SignificanceThe saying "no two leaves in the world are identical" holds philosophical significance, as such variation encompasses considerable contingency and randomness. Here, we assert that no two trees have identical leaves; meaning that even for plants of the same species and cultivar, the leaf morphology of each individual plant is distinct at the population level, even though single leaves may overlap in appearance. Genetic, environmental, and developmental information is recorded in some manner within the phenotypic appearance of leaves. With advancements in computational technologies like artificial intelligence, this information can now be decoded. HighlightsO_LIThe leaves of each individual plant are statistically unique. C_LIO_LIThe relationship between leaflet appearances in compound leaves hints at their developmental patterns. C_LIO_LILeaves are not necessarily bilaterally symmetric in a statistical sense. C_LIO_LILeaves from stems with different chirality (twining direction) exhibit distinct appearances. C_LI

plant biology↗

bioRxiv2025

Molecular evolution of CO2-sensing ab1C neurons underlies divergent sensory responses in the Drosophila suzukii species group

Organisms evolve behavioral and morphological traits to adapt to their ecological niches, yet the genetic basis of adaptation remains largely unknown. Drosophila suzukii has evolved a distinctive oviposition preference for ripe fruit, unlike most Drosophila species such as D. melanogaster, which prefer overripe fruit. Carbon dioxide (CO2), a metabolic volatile that increases as fruit ripens and decays, may act as a critical ecological cue shaping these preferences. Here, we focus on D. suzukii and its sister species D. subpulchrella, which shows an intermediate preference, to investigate the genetic basis of CO2 responses. We report a previously unrecognized shift in CO2-guided oviposition: D. suzukii and D. subpulchrella readily lay eggs on CO2-enriched substrates, unlike the strong aversion displayed by D. melanogaster. Electrophysiological recordings revealed a species-specific sensory tuning, characterized by an early spike in CO2-evoked neuronal firing in D. suzukii and D. subpulchrella--a temporal response feature absent in D. melanogaster. To dissect the genetic basis of this shift, we generated transgenic D. melanogaster expressing either the D. suzukii Gr63a coding sequence or the D. subpulchrella Gr63a cis-regulatory element. Remarkably, both manipulations reproduced the early onset firing pattern of CO2 sensitivity, demonstrating that either receptor function or expression can independently drive this sensitivity adaptation. Our findings reveal that evolution can shape ecological adaptation through distinct genetic mechanisms, leading to convergent physiological traits among closely related species. Author SummaryAnimals rely on their senses to locate food sources and identify suitable reproductive sites in their environment. Closely related species can evolve strikingly different preferences as they adapt to new environments. For example, the invasive fruit fly D. suzukii lays its eggs in ripe fruit, unlike most other fruit flies, such as D. melanogaster, which prefer decaying fruit. Because CO2 levels increase as fruit ripens and ferments, changes in how flies detect CO2 may have contributed to these ecological differences. We compared CO2 responses between D. suzukii and its sister species D. subpulchrella, and found that both species respond to CO2 differently from D. melanogaster: both in their oviposition preferences and neural CO2 sensitivity. By introducing either the D. subpulchrella or D. suzukii CO2 receptor gene coding sequences or regulatory regions into D. melanogaster, we found that this altered sensitivity can arise from changes either in the receptors protein-coding region or in the DNA elements that control its expression. Our results show that evolution can act through multiple genetic mechanisms to fine-tune sensory systems, revealing how subtle molecular changes can generate ecological diversity among closely related species.

evolutionary biology↗

bioRxiv2025

Diversity and distribution of the subtelomeric Y' elements across Saccharomyces cerevisiae

The subtelomeric regions of eukaryotic chromosomes harbor repeated elements that contribute to genomic plasticity and adaptation. In Saccharomyces cerevisiae, the Y elements represent a major class of subtelomeric repeats, yet their diversity and evolutionary dynamics remain incompletely characterized. Here, we analyzed Y elements across 54 S. cerevisiae strains using high-quality telomere-to-telomere genome assemblies. We detected 893 high-confidence Y elements, which we classified into 12 major clusters, revealing a broader structural diversity than previously described, including canonical short ([~]5.2 kb) and long ([~]6.7 kb) elements, intermediate-size classes (mid1 and mid2), and a novel family containing CA-rich repeats. Sequence analyses showed that open reading frames (ORFs), including those encoding the putative Y-Help1 helicase, are highly conserved within clusters, suggesting selective maintenance of functional sequences. The distribution of Y elements varied widely across strains and chromosome extremities, with some strains lacking Y entirely and others, such as the clinical ADI isolate, carrying up to 149 copies. Interstitial telomeric sequences (ITS) were variably associated with Y elements and tandem Y repeats, potentially facilitating recombination and amplification. Analysis of telomere length data further revealed that the presence of long Y' elements, but not Y elements from other clusters, at the subtelomere is correlated with shorter telomeres at the same chromosome end. Our results provide the most comprehensive catalog of S. cerevisiae Y elements to date, uncovering unexpected structural and sequence diversity, and a potentially functional role in telomere length regulation.

genomics↗