Biology subjects

Baker, M.

Publications and source records attributed to Baker, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Lens species genome assemblies reveal evolutionarily fragile chromosomes associated with pericentric inversions

The genus Lens is comprised of seven diploid species, including the cultivated crop Lentil, and six wild relatives often used in breeding programs for beneficial allele introgression. Lens species are proposed to exhibit considerable levels of genome structural variation both within and between species, which has implications for plant breeding and evolutionary genomics. Plant centromeres are key regions involved in chromosomal stability, where structural changes can be linked to meiotic abnormalities, resulting in inversions, translocations, and deletions of chromosomal segments. Fabeae centromeres are known to be diverse and do not fit the centromere drive model. The origins of this centromere diversity and the evolutionary trends remain unclear, but recent studies suggest that centromere structural variation plays a role in creating new sequence combinations that contribute to the unique centromere evolution patterns observed in legumes. We sequenced, assembled, and performed gene synteny analysis in the genomes of all seven Lens species using long-read sequencing technologies. We also located and characterized the centromeres in these genomes through ChIP-seq experiments to better understand their role in Lens chromosomal stability. Synteny analysis reveals that Lens genomes have undergone extensive rearrangements during evolution, with multiple translocations and inversions identified between species. Specific Lens chromosomes appear more susceptible to rearrangements over time. These same chromosomes also exhibit higher rates of rearrangement throughout Lens speciation. Fragile chromosomes are associated with the occurrence of pericentric inversions, likely disrupting stability. The diversity in satellite sequences in Lens centromeres likely results from structural changes accumulated throughout Lens evolution. These findings suggest that genome and centromere structure play significant roles in generating centromere diversity within this legume genus.

genomics↗

bioRxiv2026

SVPopEx: Population-Wide Visualization and Exploration of Structural Variants

Structural variants (SVs) are large-scale genomic variants, which can disrupt important functional and regulatory elements, leading to genomic disorders in humans and playing important roles in domestication, disease resistance, and traits in plants. SVs are generated across populations of individuals and used for association studies, consisting of large datasets with thousands of genomic loci. Visualization of these SVs aids in understanding their genomic distribution, identifying patterns across affected or phenotypic groups, and assessing their proximity to other genomic regions of interest. A variety of tools exist for visualizing SVs, including linear genome browsers and graph-based methods; however, many do not offer intuitive or scalable representations of SVs across large populations. To address this, we present SVPopEx, an interactive tool for population-wide visualization and exploration of SVs. SVPopEx provides a unique and intuitive representation for insertions, deletions, inversions, duplications, and translocations in a linear genome-style browser. Novel features were developed to support comparisons across genomes within user-defined regions, including rendering SVs based on one or more samples and visualizing haplotypes. Use of the tool is demonstrated with SV datasets from Schistosoma mansoni and Lens culinaris. A task-based evaluation was conducted using SVPopEx and two other linear genome browsers, which demonstrated that SVPopEx excelled in (1) providing a clear representation of the SVs present and (2) supporting comparisons across genomes.

bioinformatics↗

bioRxiv2026

The Role of Photoperiod, Light Intensity, and Iron Concentration on Cellular Physiology Photophysiology, and Proteomics in Southern Ocean Phytoplankton.

Primary production in the Southern Ocean (SO) plays a critical role in regulating the global carbon cycle, yet the physiological mechanisms governing phytoplankton responses to iron (Fe) limitation and variable light remain poorly constrained. Using a custom made incubation system that simulated natural diel solar variability, we examined the interactive effects of Fe availability, light intensity, and photoperiod (continuous vs. variable) on three ecologically important SO phytoplankton: Fragilariopsis cylindrus, Phaeocystis antarctica, and Thalassiosira antarctica. Physiological, photophysiological, and proteomic measurements revealed that Fe availability was the dominant factor regulating growth, carbon production, photosynthetic performance and protein expression across all species. Distinct acclimation strategies emerged: F. cylindrus exhibited marked trade-offs between productivity and photoprotection under Fe stress, consistent with adaptation to stable, low-light, Fe-poor environments; P. antarctica maintained growth by flexibly modulating photoprotective and photosynthetic capacity, reflecting high plasticity suited to dynamic, open-ocean conditions; and T. antarctica expressed a balanced strategy, sustaining productivity and photoprotection simultaneously, characteristic of coastal bloom formers with higher Fe demand. Dynamic light regimes produced smaller, species-specific effects, influencing chlorophyll content and carbon storage primarily in T. antarctica. Correlation and z-score analyses demonstrated that Fe-rich photosynthetic proteins co-varied with biomass production, whereas photoprotective traits clustered independently, underscoring divergent energy-allocation strategies. Together, these results reveal how SO phytoplankton partition resources between productivity and photoprotection under shifting Fe-light regimes, providing mechanistic insight into their ecological niches.

ecology↗

bioRxiv2026

Systemic interindividual epigenetic variants link periconceptional environment to human fetal development

At rare human genomic regions, DNA methylation states are established in the early embryo and maintained during cellular differentiation, yielding systemic (i.e. not tissue-specific) interindividual epigenetic variation. Previous screens for such correlated regions of systemic interindividual variation (CoRSIVs) were limited to White Americans. Here, we describe the first human CoRSIV screen including self-identified Black and White Americans. We integrate deep whole-genome bisulfite sequencing data for three tissues from each of ten Black and ten White donors in the NIH Genotype-Tissue Expression program. This approach identifies twice as many CoRSIVs among Black than White Americans. Establishment of CoRSIV methylation is sensitive to periconceptional environmental exposures including assisted reproduction, seasonal variation, and famine. CoRSIV-associated genes are enriched for GWAS variants linked to cancer and neurodevelopment. Although only 15% of Black CoRSIVs overlap with those among White individuals, both sets are associated with the same subfamilies of transposable elements. Within multiple cell lines, ranked enrichments of transcription factor binding to Black and White CoRSIVs are exquisitely coordinated and related to genome organization, indicating that CoRSIV methylation states established in the early embryo play an important role in guiding subsequent cellular differentiation.

Molecular Biology↗

bioRxiv2026

Phylogenomic coupling of F1 chemosensory and archaellum systems across archaea and monoderm bacteria

Archaellum-associated motility has been viewed as solely archaeal, yet new findings in Chloroflexota prompt a broader perspective. By analysing a curated [~]22,000 NCBI reference genomes alongside 2,397 archaeal and 226 archaellum-encoding Chloroflexota genomes, this study systematically characterises the co-distribution of archaellum loci with chemosensory system (CSS) classes. Maximum-likelihood phylogeny of 3,727 F1-type CheA proteins reveals three major clades, with Clade 1 comprising [~]80% monoderm representation, uniting archaeal and monoderm bacterial lineages in a shared evolutionary grouping. Overall, this work shows that not only archaeal-type motility, but also F1-CSS based sensing system, might have been gained from Archaea to Chloroflexota via horizontal gene transfer and both systems shared an evolutionary trajectory altogether.

bioinformatics↗

bioRxiv2026

A novel pathosystem between Aeschynomene evenia and Aphanomyces euteiches reveals new immune components in quantitative legume root-rot resistance.

Legumes are pivotal for sustainable agriculture, yet their productivity is hindered by soilborne pathogens such as Aphanomyces euteiches. This study introduces Aeschynomene evenia as a novel model to investigate legume immunity and its interplay with Nod factor-independent symbiosis (NFIS). Inoculation of A. evenia accessions with A. euteiches strains revealed a range of quantitative resistance levels. Phenotypic and cytological analyses showed a compatible interaction, including root browning, intracellular colonisation, and oospore production; along with partial resistance traits such as phenolic accumulation at the endodermal barrier. Transcriptomic analyses at 1 and 3 dpi identified 3,403 differentially expressed genes (DEGs), with upregulated genes associated with pathogen perception, immune signalling and specialised metabolite biosynthesis. Kinase-mediated signalling, ROS homeostasis, and WRKY transcription factors were among the most enriched functional categories. Comparative transcriptomics with Medicago truncatula confirmed conserved immune responses, while A. evenia displayed broader transcriptional repression. Integration with symbiotic transcriptomic data revealed overlapping gene signatures, including AeRLCK2 and AeCRK, previously found to be NFIS-specific, as putative dual-function kinases. Aerlck2 and Aecrk mutants exhibited enhanced resistance to A. euteiches, supporting their roles in immune regulation. This work positions A. evenia-A. euteiches as a valuable system to dissect legume quantitative resistance and its intersection with symbiosis.

plant biology↗

bioRxiv2025

Generalized brain-state modeling with KenazLBM

The large-scale functional state of a human brain remains difficult to characterize, much less predict. Regardless, techniques have been engineered to electrically neuromodulate the brain to treat a subset of neurologic and psychiatric disorders with moderate efficacy. Accurate characterization of a brains instantaneous functional state has stymied the development of more effective neuromodulation paradigms. Advanced computational methods are required to address this gap and enable large-scale neuroscience. Here we define the concept of generalized brain-state modeling across humans as Large Brain-State Modeling (LBM) and present KenazLBM as the worlds first example. KenazLBM can instantaneously characterize the functional state of a persons brain with raw iEEG data, and predict future brain-states. KenazLBM was trained on over 17.9 billion unique multichannel tokens from people undergoing intracranial electroencephalography (iEEG) recordings, and has learned to interrelate brain-states between people into a common interpretable topology. Most importantly, the model generalizes to unseen subject data with significant recording channel heterogeneity from the training set. We offer KenazLBM as a first generalized brain-state model to serve as a new paradigm of basic neuroscience inquiry and potential translation into neuromodulation therapeutics.

neuroscience↗

bioRxiv2025

Development of a Nested Association Mapping (NAM) population for untangling complex traits in lentil (Lens culinaris Medik.)

Understanding the genetic basis of complex traits remains a key challenge in crop improvement. This study aimed to develop a structured, multi-parental mapping population to enhance the resolution of quantitative trait dissection, based on the hypothesis that a Nested Association Mapping (NAM) design would enable the detection of minor-effect loci often overlooked by traditional biparental or diversity panel-based approaches. A lentil (Lens culinaris Medik.) NAM population was developed by crossing the Canadian cultivar CDC Redberry with 32 diverse genotypes sourced globally from three major lentil-growing macro-environments: Northern temperate, Mediterranean, and South Asia. The resulting recombinant inbred lines were phenotyped for key phenological traits, days to emergence (DTE), flowering (DTF), and maturity (DTM), under field conditions, and genotyped using exome capture sequencing. Genome-wide association studies for DTF identified 14 significant loci across six chromosomes, including the known FTb locus and novel associations near AP3a, HUB2a, and PIF6 genes. These results demonstrate the utility of the NAM design in detecting both major and minor-effect loci that underlie complex trait variation. To our knowledge, this is the first publicly available NAM population in lentil. It provides a high-resolution, globally representative platform for trait discovery, pre-breeding, and collaborative genetic improvement of this nutritionally and agronomically important legume.

plant biology↗

bioRxiv2025

SF3B1K700E Drives Oncogenic Alternative Splicing of Cell Cycle Checkpoint Genes in Cancer

Pre-mRNA splicing plays a crucial role in maintaining cellular homeostasis, with strict regulation required for processes such as cell cycle progression. SF3B1, a core component of the spliceosome, has emerged as a key player in alternative splicing regulation and is frequently mutated in cancer. Among these mutations, SF3B1K700E disrupts normal splicing patterns and deregulates cell cycle control. Here we profiled K562 erythroleukaemia cells expressing either wild-type or SF3B1K700E by RNA-seq and uncovered 763 high-confidence splicing alterations enriched for G2/M regulators, including ARPP19, ENSA, STAG2 and ECT2. Notably, increased inclusion of ARPP19 exon 2 produces the ARPP19-long isoform, which sustains PP2A-B55 inhibition and promotes mitotic progression. A core subset of the K700E-linked splicing changes re-appeared after siRNA-mediated SF3B1 depletion in HeLa cells, underscoring a mutation-dependent spliceosomal signature that transcends cell type. Pharmacological inhibition of DYRK1A (INDY) or broad serine/threonine phosphatases (okadaic acid) shifted ARPP19 exon 2 inclusion in the same direction as SF3B1K700E, pointing to a kinase-phosphatase signaling axis that influences these splice events. Functionally, ectopic expression of ARPP19-long accelerated mitotic exit, and high ARPP19-long abundance associated with poorer overall survival in the TCGA-AML cohort. Our findings highlight a connection between SF3B1-dependent splicing, cell cycle progression, and tumorigenesis, offering new insights into the molecular mechanisms underlying cancer-associated splicing dysregulation.

molecular biology↗

bioRxiv2025

Exploring fern pathosystems and immune receptors to bridge gaps in plant immunity

Land plants include angiosperms, bryophytes, lycophytes and ferns, each of which may deploy distinct strategies to resist pathogens. Here, we investigate fern-pathogen interactions by characterizing novel pathosystems and analysing the diversity of fern immune receptors. A collection of fern species was inoculated with a diverse set of microbes, and disease symptoms were assessed. We further leveraged published genome mining tools to analyse the diversity of RECEPTOR-LIKE KINASES, RECEPTOR-LIKE PROTEINS (RLKs/RLPs) and NUCLEOTIDE-BINDING AND LEUCINE-RICH REPEATS (NLRs), along with key immune signalling components, in ferns. Our results reveal that ferns exhibit a range of responses to pathogens, including non-host resistance and specific resistance mechanisms. Among ten ferns tested, Pteris vittata displays the broadest spectrum of pathogen compatibility. Genome mining indicates that ferns encode a diverse repertoire of putative immune receptors, antimicrobial peptides and mediators of systemic acquired resistance. Ferns possess numerous RLKs/RLPs, resembling those required for cell-surface immunity in angiosperms. They also encode diverse NLRs, including a previously undescribed class with a disordered N-terminal domain, termed disN-NLR. These findings provide insights into disease resistance evolution and open promising perspectives for crop protection strategies.

plant biology↗

bioRxiv2023

Tertiary-interaction characters enable fast, model-based structural phylogenetics beyond the twilight zone

Protein structure is more conserved than protein sequence, and therefore may be useful for phylogenetic inference beyond the "twilight zone" where sequence similarity is highly decayed. Until recently, structural phylogenetics was constrained by the lack of solved structures for most proteins, and the reliance on phylogenetic distance methods which made it difficult to treat inference and uncertainty statistically. AlphaFold has mostly overcome the first problem by making structural predictions readily available. We address the second problem by redeploying a structural alphabet recently developed for Foldseek, a highly-efficient deep homology search program. For each residue in a structure, Foldseek identifies a tertiary interaction closest-neighbor residue in the structure, and classifies it into one of twenty "3Di" states. We test the hypothesis that 3Dis can be used as standard phylogenetic characters using a dataset of 53 structures from the ferritin-like superfamily. We performed 60 IQtree Maximum Likelihood runs to compare structure-free, PDB, and AlphaFold analyses, and default versus custom model sets that include a 3DI-specific rate matrix. Analyses that combine amino acids, 3Di characters, partitioning, and custom models produce the closest match to the structural distances tree of Malik et al. (2020), avoiding the long-branch attraction errors of structure-free analyses. Analyses include standard ultrafast bootstrapping confidence measures, and take minutes instead of weeks to run on desktop computers. These results suggest that structural phylogenetics could soon be routine practice in protein phylogenetics, allowing the re-exploration of many fundamental phylogenetic problems.

evolutionary biology↗

bioRxiv2023

Avian influenza viruses in wild birds in Canada following incursion of the highly pathogenic H5N1 virus from Eurasia in 2021/2022

Following detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada in late 2021, avian influenza surveillance in wild birds was scaled-up across Canada. Herein, we present results of Canadas Interagency Surveillance Program for Avian Influenza in wild birds during the first year (November 2021 - November 2022) following the incursions of HPAIV from Eurasia. Key objectives of the surveillance program were to (i) detect the presence, distribution and spread of HPAIV and other avian influenza viruses (AIVs), (ii) detect wild bird morbidity and mortality associated with HPAIV, (iii) identify the range of wild bird species infected by HPAIV, and (iv) characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across One Health partners.

zoology↗

bioRxiv2023

Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China

Sharing among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 E. coli and S. enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance in Escherichia coli and susceptibility in Salmonella enterica. Many of these genes were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

genomics↗

bioRxiv2023

CEP76 is a critical regulator of male germ cell transition zone function and tail composition

The transition zone is a specialised gate at the base of cilia/flagella, which segregates the ciliary compartment from the cytoplasm and strictly regulates protein entry. In this study, we have identified CEP76 as an essential germ cell transition zone protein, involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail. In its absence sperm tails are shorter and immotile as a consequence of deficits in essential sperm motility proteins including DNAH2 and AKAP4, which accumulate at the sperm neck in the mutant. We demonstrate CEP76 is required for sperm tail fibrous sheath formation, outer dense fibre loading and axoneme stability in the principal piece and ultimately sperm motility. Finally, we identify that CEP76 dictates annulus positioning and composition, adding further evidence that the spermatid transition zone and annulus are part of the same functional structure.

cell biology↗

bioRxiv2022

Hematopoiesis and cell growth are differentially regulated by TAL1 isoforms

T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is a common cause of T-ALL. Here we studied the two protein isoforms of TAL1, short and long, that are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5 UTR with differential regulation of translation. Moreover, our study suggests that the enhancers regulate TAL1 exon 3 alternative splicing by inducing changes in the chromatin at the splice site, which we demonstrate is mediated by KMT2B. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and functions as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, when we expressed both isoforms in mice bone-marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone leads to hematopoietic stem cell exhaustion. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the CML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoforms ratio could be a preferred therapeutic approach.

molecular biology↗

bioRxiv2022

Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer's Disease related proteins

Alzheimers disease (AD) is neuropathologically characterized by amyloid-beta (A{beta}) plaques and neurofibrillary tangles. Main protein components of these hallmarks include A{beta}40, A{beta}42, tau, phospho-tau and APOE. With the exception of the APOE-{varepsilon}4 variant, genetic risk factors associated with brain biochemical measures of these proteins have yet to be characterized. We performed a genome-wide association study in brains of 441 AD patients for quantitative levels of these proteins collected from three distinct fractions reflecting soluble, membrane-bound and insoluble biochemical states. We identified 123 genome-wide significant associations at seven novel loci and the APOE locus. Genes and variants at these loci also associate with multiple AD- related measures, regulate gene expression, have cell-type specific enrichment, and roles in brain health and other neuropsychiatric diseases. Pathway analysis identified significant enrichment of shared and distinct biological pathways. Although all biochemical measures tested reflect proteins core to AD pathology, our results strongly suggest that each have unique genetic architecture and biological pathways that influence their specific biochemical states in the brain. Our novel approach of deep brain biochemical endophenotype GWAS has implications for pathophysiology of proteostasis in AD that can guide therapeutic discovery efforts focused on these proteins.

genetics↗

bioRxiv2022

Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control

Waste from dairy production is one of the worlds largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs). However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with >99% reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for prevalence and control of AMR, and that measures to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.

microbiology↗

bioRxiv2022

Mechanical strain stimulates COPII-dependent trafficking via Rac1

Secretory trafficking from the endoplasmic reticulum (ER) is subject to regulation by extrinsic and intrinsic factors. While much of the focus has been on biochemical triggers, little is known whether and how the ER is subject to regulation by mechanical signals. Here, we show that COPII-dependent ER-export is regulated by mechanical strain. Mechanotransduction to the ER was mediated via a previously unappreciated ER-localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulate ER-to-Golgi transport. Altogether, we establish an unprecedented link between mechanical strain and export from the ER.

cell biology↗