Biology subjects

Lian, Q.

Publications and source records attributed to Lian, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolutionary diversification of the SymRK receptor family in land plants

Plant receptor-like kinases (RLKs) are involved in diverse processes, ranging from growth and reproduction to interactions with microbes. Variation in the extracellular domains delineates several RLKs subfamilies, including the malectin-like domain leucine-rich repeat receptor-like kinases (MLD-LRR-RLKs). Symbiosis Receptor-like Kinase (SymRK) is the prototypical member of MLD-LRR-RLKs and is required for microbial accommodation in host roots during root endosymbiosis. Yet, comparative phylogenetic analysis of SymRK orthologs in the broader context of MLD-LRR-RLK subfamily evolution remains limited. In this study, we examined the inventory, phylogeny and clade-specific evolutionary and transcriptional characteristics of this receptor group. SymRK and its closest homologs are present in most land plant lineages and group into four major clades and six additional species-specific clades. These clades can be distinguished by their evolutionary characteristics as either conserved with reduced gene copy number changes (including SymRK) or expanded and diversified, as observed in clade IV. Clade IV dynamics are largely driven by tandem gene duplications, which often arise within gene clusters. We further analysed the evolutionary characteristics of MLD-LRR-RLKs at the population level in Arabidopsis thaliana accessions. We found that some genes are conserved across accessions and are therefore likely to be functionally important, whereas a subset of genes, often located within tandem clusters, are highly diverse and likely contribute to accession-specific adaptations. Finally, most MLD-LRR-RLKs in the A. thaliana Col-0 accession are expressed in roots and respond broadly to biotic stimuli at the transcriptional level. Notably, clustered genes frequently exhibited divergent expression profiles, suggesting transcriptional diversification. Together, we revealed two contrasting evolutionary characteristics among members of the MLD-LRR-RLK subfamily, potentially associated with their functions in plants.

plant biology↗

bioRxiv2026

VeloTrace Reconciles Divergent Velocity and Trajectory in Single-cell Transcriptomics with Deep Neural ODE

Cellular identity and fate transitions are governed by continuous molecular processes that form dynamic trajectories within a high-dimensional transcriptomic landscape. Existing methods attempt to model these dynamics from two complementary perspectives: trajectory inference and velocity modeling. Ideally, velocity and trajectory are dual aspects of transcriptomic dynamics where velocity is tangent to trajectory everywhere. This inherent connection between velocity and trajectory is currently absent in transcriptomic analysis. Splicing velocity are precision-limited to inadequately-sequenced genes, while trajectory inference prioritizes the modeling of global trends while omitting local dynamics. This divergence breaks the geometric continuity between local velocities and global trajectories, hindering the reliable interpretation of developmental dynamics. To reconcile trajectory inference and RNA velocity, we introduce VeloTrace, a framework that unifies them through Neural Ordinary Differential Equations (NeuralODEs). VeloTrace learns a continuous-time velocity field whose integral curves constitute the trajectory itself, while ensuring that velocities are tangent to integral paths everywhere. Leveraging a splicing quality score, VeloTrace incorporates high-quality splicing velocity as partial supervision for velocity orientation and grounding. During optimization, VeloTrace incorporates a Monte Carlo multi-time-frame supervision strategy to ensure coherence between local and global trajectorys and suppress sequencing-induced stochastic diffusion. Through refining the velocity field and cell-specific parameters for pseudo-time, expression, and velocity, VeloTrace reconstructs a smooth, local-and-global-coherent velocity-vector-guided flow in the transcriptomic latent space. This strategy ensures a complementary integration of velocity and trajectory, imputing the transcriptional kinetics for genes of insufficient strength, whose kinetics cannot be accurately portrayed by splicing velocity. In simulation benchmarks, VeloTrace captured the transcriptional dynamics of all expressed genes, even those with inadequate sequencing coverage, producing velocity directions that were most consistent with the true direction and every-where tangential across the entire process, outperforming state-of-the-art methods, including scVelo, UniTVelo, VeloVI and scTour. VeloTrace uniquely reconciles RNA velocity and trajectory inference, creating a velocity field where each cell can infer past and future transitions from its current state. Moreover, VeloTrace extends reliable velocity estimation to a broader set of genes. When applied to mouse neural stem cell differentiation data, it successfully recovers dynamics of driver genes for two developmental lineages, including those with low expression, shedding light on their regulatory roles during differentiation. This unified framework lays the foundation for more accurate modeling of gene regulation and cell fate decisions in complex biological systems.

bioinformatics↗

bioRxiv2026

NORAD orchestrates KLC1-mediated SFPQ transport via liquid-liquid phase separation

Neuronal function requires precise long-distance axonal transport mediated by molecular motors and RNA-binding proteins like SFPQ, though regulatory mechanisms remain poorly defined. We identify long non-coding RNA NORAD as a master regulator of this process through liquid-liquid phase separation (LLPS). While SFPQ and kinesin-1 mediate cargo delivery, the specific RNA coordinating their interaction was unknown. We demonstrate NORAD directly binds kinesin light chain 1 (KLC1) and promotes SFPQ condensation into dynamic LLPS droplets, enabling efficient transport. CRISPR-assisted mapping and functional assays show NORAD depletion disrupts granule dynamics, impairs neuroprotective mRNA localization, and induces axonal degeneration. In vitro reconstitution confirms NORAD-KLC1 synergy enhances SFPQ phase separation, and neuron-specific knockout mice exhibit motor deficits with reduced neuronal density. These findings establish the first evidence of lncRNA NORAD-mediated LLPS in axonal transport, revealing a new paradigm for RNA-guided neuronal maintenance.

molecular biology↗

bioRxiv2025

Chromosome-scale Solanum pennellii and Solanum cheesmaniae genome assemblies reveal structural variants, repeat content and recombination barriers of the tomato clade

Crop wild relatives are important resources for improving cultivated crops, yet the precise introgression of wild genetic material into cultivated crops is often difficult and cannot be fully defined without high-quality genome assemblies. Here we used PacBio HiFi, ONT ultra-long and Hi-C sequencing approaches to generate chromosome-scale de novo genome assemblies of two wild species related to the domesticated tomato (Solanum lycopersicum) -- the broadly stress-resistant Solanum pennellii (accession LA0716) and the salt-resistant Solanum cheesmaniae (accession LA1039). K-mer and BUSCO analysis of both assemblies demonstrated above 99% completeness and the improved S. pennellii genome adds 146 Mbp to the 12 chromosomes compared with the original reference. We aligned the new assemblies with seven gold-standard assemblies from the Lycopersicon clade, using Solanum tuberosum as an outgroup, and identified shared and species-specific structural variants. The repeat content of all nine assemblies was characterized, providing evidence for independent explosions of Tekay (gypsy superfamily) retrotransposons in S. pennellii and S. peruvianum. Whole genome sequencing of 709 recombinant plants derived from male and female backcrosses of three different hybrids (S.pennellii, S. cheesemaniae and Solanum lycopersicum cv. Micro-Tom crossed with Solanum lycopersicum cv. Moneyberg-TMV) revealed higher crossover rate in female meiosis. Recombination landscape analysis identified conserved female-enhanced recombination regions, and coldspots that were completely devoid of meiotic crossovers including megabase-scale inversions and insertion-deletion polymorphisms between S. lycopersicum and S. pennellii. In summary, we harnessed our high-quality S. pennellii and S. cheesmaniae genome assemblies to reveal how repeat content diverged in nature and during breeding, and uncovered how reproductive gender interacts with structural variants to dictate the recombination landscape in tomato hybrids.

plant biology↗

bioRxiv2025

A dual-metric framework for quantifying the biological fidelity of scRNA-seq pipelines

Single-cell RNA sequencing (scRNA-seq) enables high-resolution transcriptional profiling, but early-stage processing pipelines differ markedly in barcode recovery, UMI correction, and read assignment-variations that can propagate and bias downstream analyses. We present a reproducible, parameter-aware benchmarking framework to quantify the biological fidelity of four primary pipelines-STARsolo, Cell Ranger, Kallisto|Bustools, and Alevin-fry-across simulated ground-truth datasets and complex biological contexts, including a Huntingtons disease (HD) mouse model. Our approach introduces two complementary metrics: the Cluster Annotation Score (CAS), assessing concordance between direct cell-level and cluster-level consensus labels, and the Marker Concordance Score (MCS), measuring cohesion of de novo marker genes per cell type. By systematically varying highly variable gene (n_HVG) and principal component (n_PC) settings, we map how upstream quantification interacts with downstream parameter choice. Simulations show STARsolo and Kallisto|Bustools deliver high technical accuracy, but only STARsolo consistently preserves stable cell identities and coherent marker expression across parameter regimes. In empirical datasets, alignment-based pipelines (STARsolo, Cell Ranger) yield higher CAS/MCS values and more biologically faithful annotations, while alignment-free methods show reduced signal fidelity despite faster runtimes. Differences introduced during primary processing persist after batch correction and integration, altering disease-associated cell type detection. Our open-source CAS-MCS-Scoring toolkit enables transparent evaluation of pipeline performance, providing a practical guide for selecting analysis strategies that maximize reproducibility and biological interpretability in scRNA-seq studies.

bioinformatics↗

bioRxiv2025

Polymorphism can extensively reshape the genome-wide crossover landscape in Arabidopsis thaliana.

Meiotic recombination, via the formation of crossovers (COs), re-assorts parental alleles and dictate which traits are inherited together, or not. The recombination rate is not homogeneous across the genome, and uncovering the causes of these fluctuations can inform our understanding of DNA recombination and genome evolution. In this study we show that presence of sequence divergence (polymorphism) between homologous chromosomes increases the local recombination rate in Arabidopsis thaliana. This effect is observed genome-wide, turning cold regions of the genome hot. This relocation of COs towards polymorphic regions occurs at the expense of non-polymorphic ones, which become colder. This global overhaul of the CO landscape is dependent on the mismatch repair (MMR) machinery. This suggests that MMR has a pro-CO role, driving COs to regions of the genome where it could detect sequence differences between homologous chromosomes. Our study demonstrates that polymorphism can be a major recombination driver in A. thaliana.

genetics↗

bioRxiv2025

Unlocking meiotic crossovers near plant centromeres

Crossovers (COs) ensure proper chromosome segregation during meiosis and generate genetic diversity. COs are non-uniformly distributed along chromosomes and almost universally suppressed in centromere-proximal regions, notably creating a significant bottleneck for plant breeding. The mechanism of this CO suppression is elusive, but chromatin state is a contributing factor. Here, we identify three factors that actively limit proximal CO in Arabidopsis, the cohesion establishment factor CTF18, the centromeric cohesin protector SGO2, and the deSUMOylase SPF2. The mutation of these factors allows both the formation of CO in centromere-proximal region where they were completely absent in the wild-type, and enhance their frequency where they were rare. COs can be further increased by combining these mutations together or with mutation in the DNA methylase CMT3, suggesting that multiple mechanism prevent proximal CO in parallel. The identification of the very conserved CTF18, SGO2 and SPF2 as suppressors of centromere-proximal CO highlights the importance of cohesin turnover in this process and opens up new possibilities for plant breeding.

genetics↗

bioRxiv2025

Integrating multi-modal transcriptomics identifies cellular subtypes with distinct roles in PDAC progression

BackgroundPancreatic ductal adenocarcinoma (PDAC) features a complex tumor microenvironment (TME) that significantly influences patient outcomes. Understanding the TMEs cellular composition and interactions is crucial for identifying therapeutic targets to improve treatment. MethodsWe performed an integrative analysis combining 88 single-cell RNA sequencing (scRNA-seq) samples with 187,520 cells, 20 Visium spatial transcriptomics (ST-seq) samples with 67,933 spots, and 1383 bulk RNA-seq samples and 2 Xenium high-resolution ST-seq samples with 307,679 cells, to delineate and characterize distinct subpopulations of fibroblasts, macrophages, T/NK cells, and B/plasma cells within the PDAC microenvironment. Correlations among major cell types across 12 PDAC datasets were assessed through gene set variation analysis (GSVA). Kaplan-Meier survival analysis was used to evaluate the prognostic significance of cell subtypes. Furthermore, multiplex immunohistochemistry (mIHC) and the Xenium platform was utilized to validate cellular interactions in human PDAC tissues at both protein and RNA levels. ResultsSix fibroblast subtypes and eight macrophage/monocyte subtypes were identified. POSTN high fibroblasts and SPP1 high macrophages highly infiltrated tumor tissues and were associated with poor prognosis. Most immune cell subtypes mediate adverse prognoses, except for CCL4 high CD8+ T EFF cells and IGHG1 high plasma cells, which are linked to favorable outcomes. ST-seq revealed spatial colocalization of POSTN high Fibro and SPP1 high Macro cells, as well as CCL4 high CD8+ T EFF and IGHG1 high plasma cells. These findings were corroborated by mIHC and validated using Xenium spatial transcriptomics with single-cell resolution, which confirmed the expression and spatial proximity of these markers at both the gene and protein levels. ConclusionThis integrative analysis of the PDAC TME underscores the prognostic importance of POSTN high fibroblasts and SPP1 high macrophages, while also highlighting the protective roles of CCL4 high CD8+ T EFF cells and IGHG1 high plasma cells. These insights could improve PDAC treatment strategies.

cancer biology↗

bioRxiv2024

The 1001G+ project: A curated collection of Arabidopsis thaliana long-read genome assemblies to advance plant research

Arabidopsis thaliana was the first plant for which a high-quality genome sequence became available. The publication of the first reference genome sequence almost 25 years ago was already accompanied by genome-wide data on sequence polymorphisms in another accession, or naturally occurring strain. Since then, inventories of genome-wide diversity have been generated at increasingly precise levels. High-density genotype data for A. thaliana, including those from the 1001 Genomes Project, were key to demonstrating the enormous power of GWAS in inbred populations of wild plants, and the comparison of intraspecific polymorphism with interspecific divergence has illuminated many aspects of plant genome evolution. Over the past decade, an increasing number of nearly complete genome sequences have been published for many more accessions. Here, we highlight the diversity of a curated collection of previously published and so far unpublished genome sequences assembled using different types of long reads, including PacBio Continuous Long Reads (CLR), PacBio High Fidelity (HiFi) reads, and Oxford Nanopore Technologies (ONT) reads. This 1001 Genomes Plus (1001G+) resource is being made available at http://1001genomes.org. We invite colleagues with yet unpublished genome assemblies from A. thaliana accessions to contribute to this effort.

genomics↗

bioRxiv2024

Maximizing meiotic crossover rate reveals the map of Crossover Potential

Meiotic crossovers are limited in number and unevenly distributed along chromosomes, both features often differing between sexes. The mechanisms imposing a different crossover landscape in female and male meiosis remain elusive. Here, we simultaneously disrupted multiple anti-crossover mechanisms in Arabidopsis and analyzed the whole genome sequence of thousands of female- and male-derived progenies. The largest crossover increase was reached in zyp1 recq4, with 12-fold in females and a 4.5-fold increase in males. Despite this unprecedented level of crossovers, fertility is marginally affected, opening new possibilities for plant breeding. Manipulating additional crossover regulators in zyp1 recq4 did not further elevate the frequency of crossovers, but modified the relative contributions of the two known crossover pathways. This suggests an upper limit was reached and the two pathways compete for a large but limited set of recombination intermediates. Remarkably, while wild-type crossover distribution differs markedly between sexes, the crossover landscapes of diverse mutants in both females and males converge to a single novel profile, which we termed Crossover Potential (COP). The COP profile, which we defined using 49,482 crossovers, can be accurately predicted using only sequence divergence and chromatin features. We propose that the COP represents the density of eligible recombination precursors, which is determined by genomic features and is thus identical in females and males. It suggests that the sexual dimorphism in the crossover landscape results exclusively from differential regulation of the likeness of precursors to mature into crossovers.

genetics↗

bioRxiv2024

MutLgamma enforces meiotic crossovers in Arabidopsis thaliana

During meiosis, each chromosome pair experiences at least one crossover (CO), which directs their balanced segregation in addition to shuffling genetic information. COs tend to be away from each other, a phenomenon known as CO interference. The main biochemical pathway for CO formation, which is conserved in distant eukaryotes, involves the ZMM proteins together with the MLH1-MLH3 complex (MutL{gamma}). Here, we aim to clarify the role of MutL{gamma} in CO formation in Arabidopsis thaliana. We show that AtMutL{gamma} is partially dispensable for ZMM-dependant CO formation. HEI10 large foci - that mark CO sites in wild-type-form at a normal level in mlh1 and mlh3 mutants, but are inefficiently maturated into COs. Mutating the MUS81 nuclease in either mlh1 or mlh3 leads to chromosome fragmentation, which is suppressed by further mutating the zmm msh5. This suggests that in the absence of MutL{gamma}, recombination intermediates produced by ZMMs are resolved by MUS81, which does not ensure CO formation. Finally, CO interference is not affected in mlh1, which is compatible with a random sub-sampling of normally patterned CO sites. We conclude that AtMutL{gamma} imposes designated recombination intermediates to be resolved exclusively as COs, supporting the view that MutL{gamma} asymmetrically resolves double-Holliday junctions, yielding COs.

genetics↗

bioRxiv2024

AAB-seq: An antigen-specific and affinity-readable high-throughput BCR sequencing method

B-cell receptor (BCR) sequencing is a powerful antibody discovery tool but current methodology is often inefficient, and lead generation often requires the production and testing of numerous antibody candidates, and it is difficult to provide affinity information for their antibodies at the same time. Here, we introduce AAB-seq (antigen affinity-readable High-throughput BCR sequencing), an efficient antibody screening tool to identify antigen binding affinity of thousands of paired BCRs. It employs fluorophore and DNA barcode-labeled antigen and secondary antibody targeting Ig light chain to label B cells and uses high throughput single cell BCR sequencing and surface protein profiling to obtain the ratio of surface bound antigen to surface BCR in thousands of B-cells. Using AAB-seq, we accurately identified valuable candidate antibodies 1743-3 and 1743-13 from SARS-CoV-2 RBD immunized mouse, providing a basis for further development of SARS-CoV-2 antibody drugs. Thus, AAB-seq allows high throughput identification of antibody sequences paired with antigen affinity, which improves the screening efficiency of functional antibodies and provides an effective solution for the rapid discovery and development of new therapeutic monoclonal antibodies.

immunology↗

bioRxiv2024

Elevated Activity in Left Homologous Music Circuits is Maladaptive for Music Perception but Mediated by Decoupled Structure and Function

Music is inherent in human life and is a significant topic of cognitive neuroscience. Previous studies focused on amusia suggested that two frontotemporal circuits engage in music processing. Structure-function coupling is an important feature of human brain, which is associated with cognition and allows for a more sensitive investigation of brain-behavior association. However, we still have limited knowledge about the relation between structure-function coupling, music processing and other regional neural profiles. We recruited 106 participants (43 subjects were diagnosed with congenital amusia) and measured their music perception by Montreal Battery of Evaluation of Amusia (MBEA). Then we utilized support vector regression algorithm and mediation analysis, and employed amplitude of low frequency fluctuation (ALFF), structural/functional degree centrality (DC) and structure-function coupling to explore their relation with global averaged MBEA score. We found structure-function coupling of widespread brain regions in both hemispheres, rather than ALFF or DC, contributed to predict MBEA score. Left middle frontal gyrus, bilateral inferior temporal gyrus and right insula were most predictive regions, and these regions were involved in memory and cognitive control according to meta-analysis. Further, coupling of left middle frontal gyrus, a region that is homologous to and is connected with typical music circuits, fully mediated the negative relation between ALFF and MBEA score. Our findings provide further understanding for the neural basis of music, and have implications for neural plasticity, neuromodulation therapy and cognitive causes of amusia. HighlightsO_LIOur study first applies structure-function coupling to investigate the neural correlates of music perception, and predicting modeling indicate structure-function coupling is more effective than regional activity and connectivity. C_LIO_LIElevated activity of contralateral homologous of music circuits might be maladaptive rather than compensatory. C_LIO_LIElevated spontaneous regional activity disrupts their connections, which might be a specific expression of neural plasticity for certain regions. C_LIO_LIOur findings have implications for cognitive causes (abnormal memory and/or cognitive control to music salients) of amusia. C_LI

neuroscience↗

bioRxiv2023

HCCDB v2.0: Decompose the Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). By integrating 15 transcriptomic datasets of HCC clinical samples, the first version of HCCDB was released in 2018. The meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and robustness. After four years, the database needs to integrate recently published datasets. Furthermore, the latest single-cell and spatial transcriptomics provided a great opportunity to decipher the complex gene expression variations at the cellular level with spatial architecture. Here, we present HCCDB v2.0, an updated version that combines bulk, single-cell, and spatial transcriptomic data of HCC clinical samples. It dramatically expands the bulk sample size, adding 1656 new samples of 11 datasets to the existing 3917 samples, thereby enhancing the reliability of transcriptomic meta-analysis. A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections, respectively. A novel single-cell level and 2-dimension (sc-2D) metric was proposed to summarize the cell type-specific and dysregulated gene expression patterns. Results are all graphically visualized in our online portal, allowing users to easily retrieve data through a user-friendly interface and navigate between different views. With extensive clinical phenotypes and transcriptomic data in the database, we show two applications for identifying prognosis-associated cells and tumor microenvironment. HCCDB v2.0 is available at http://lifeome.net/database/hccdb2.

cancer biology↗

bioRxiv2023

Structural variation and DNA methylation shape the centromere-proximal meiotic crossover landscape in Arabidopsis

BackgroundCentromeres load kinetochore complexes onto chromosomes, which mediate spindle attachment and allow segregation during cell division. Although centromeres perform a conserved cellular function, their underlying DNA sequences are highly divergent within and between species. Despite variability in DNA sequence, centromeres are also universally suppressed for meiotic crossover recombination, across eukaryotes. However, the genetic and epigenetic factors responsible for suppression of centromeric crossovers remain to be completely defined. ResultsTo explore the centromere-proximal recombination landscape, we mapped 14,397 crossovers against fully assembled Arabidopsis thaliana genomes. A. thaliana centromeres comprise megabase-scale satellite repeat arrays that load nucleosomes containing the CENH3 histone variant. Each chromosome possesses a structurally polymorphic 3-4 megabase region where crossovers were absent, that includes the satellite arrays, flanked by 1-2 megabase low-recombination zones. The recombination-suppressed regions are enriched for Gypsy/Ty3 retrotransposons, and additionally contain expressed genes with high genetic diversity that initiate meiotic recombination, yet do not crossover. We mapped crossovers at high-resolution in proximity to CEN3, which resolved punctate centromere-proximal hotspots that overlapped gene islands embedded in heterochromatin. Centromeres are densely DNA methylated and the recombination landscape was remodelled in DNA methylation mutants. We observed that the centromeric low-recombining zones decreased and increased crossovers in CG (met1) and non-CG (cmt3) mutants, respectively, whereas the core non recombining zones remained suppressed. ConclusionOur work relates the genetic and epigenetic organisation of the A. thaliana centromeres and flanking pericentromeric heterochromatin to the zones of crossover suppression that surround the CENH3-occupied satellite repeat arrays.

genomics↗

bioRxiv2023

Benchmarking Algorithms for Gene Set Scoring of Single-cell ATAC-seq Data

Gene set scoring (GSS) has been routinely conducted for gene expression analysis of bulk or single-cell RNA-seq data, which helps to decipher single-cell heterogeneity and cell-type-specific variability by incorporating prior knowledge from functional gene sets. Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a powerful technique for interrogating single-cell chromatin-based gene regulation, and genes or gene sets with dynamic regulatory potentials can be regarded as cell-type specific markers as if in scRNA-seq. However, there are few GSS tools specifically designed for scATAC-seq, and the applicability and performance of RNA-seq GSS tools on scATAC-seq data remain to be investigated. We systematically benchmarked ten GSS tools, including four bulk RNA-seq tools, five single-cell RNA-seq (scRNA-seq) tools, and one scATAC-seq method. First, using matched scATAC-seq and scRNA-seq datasets, we find that the performance of GSS tools on scATAC-seq data is comparable to that on scRNA-seq, suggesting their applicability to scATAC-seq. Then the performance of different GSS tools were extensively evaluated using up to ten scATAC-seq datasets. Moreover, we evaluated the impact of gene activity conversion, dropout imputation, and gene set collections on the results of GSS. Results show that dropout imputation can significantly promote the performance of almost all GSS tools, while the impact of gene activity conversion methods or gene set collections on GSS performance is more GSS tool or dataset dependent. Finally, we provided practical guidelines for choosing appropriate pre-processing methods and GSS tools in different scenarios.

bioinformatics↗

bioRxiv2022

HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans

Crossovers (CO) shuffle genetic information and physically connect homologous chromosome pairs, ensuring their balanced segregation during meiosis. COs arising from the major class I pathway require the activity of a well-conserved ZMMs group of proteins which, in conjunction with MLH1, facilitate the maturation of DNA recombination intermediates specifically into COs. The HEIP1 protein was identified in rice and proposed to be a new, plant-specific member of the ZMM group. Here we establish and decipher the function of the Arabidopsis thaliana HEIP1 homolog in meiotic crossover formation and report its wide conservation in eukaryotes. We show that the loss of Arabidopsis HEIP1 elicits a marked reduction in meiotic COs and their redistribution towards chromosome ends. Epistasis analysis showed that AtHEIP1 acts specifically in the class I CO pathway. Further, we show that HEI1P acts both prior to crossover designation, as the number of MLH1 foci is reduced in heip1, and at the maturation step of MLH1-marked sites into COs. Despite the HEIP1 protein being predicted to be primarily unstructured and very divergent at the sequence level, we identified homologs of HEIP1 in an extensive range of eukaryotes, including mammals.

genetics↗

bioRxiv2022

Remarkably high rate of meiotic recombination in the fission yeast Schizosaccharomyces pombe

In most eukaryotes, the number of meiotic crossovers (COs) is limited to 1-3 per chromosome, which are prevented from occurring close to one another by CO interference. The fission yeast Schizosaccharomyces pombe, an exception to this general rule, lacks CO interference and seems to have the highest CO number per chromosome. However, global CO frequency was indirectly estimated in this species, raising doubts about this exceptional recombination level. Here, we used an innovative strategy to directly determine COs genome-wide in S. pombe. We confirm the absence of crossover interference and reveal the presence of co-variation in CO number across chromosomes within tetrads, suggesting that a limiting pro-CO factor varies stochastically between meiocytes. CO number per chromosome varies linearly with chromosome size, with the three chromosomes having, on average, 15.9, 12.5, and 7.0 COs, respectively. This is significantly lower than previous estimates but reinforces S. pombes exceptional status as the eukaryote with the highest CO number per chromosome described to date and among the species with the highest rate of COs per unit of DNA.

genetics↗