Biology subjects

Abraham, L.

Publications and source records attributed to Abraham, L..

7 recordsLinked to original sources

bioRxiv2025

Copy Number Variation: A Substrate for Plant Adaptation and Stress Response in Arabidopsis

Copy number variation (CNV) is a major source of genomic diversity that shapes gene family evolution and may contribute to ecological differentiation, yet its genome-wide ecological relevance remains poorly understood. Here, we analyzed CNV across four Brassicaceae species (Arabidopsis thaliana, A. lyrata, A. halleri, and Arabis alpina) to identify gene families undergoing rapid expansion or contraction. Using a birth-death model, we identified 231 rapidly evolving gene families spanning diverse functional categories. We then characterized CNV within populations of A. thaliana and A. lyrata using population-scale long-read assemblies. CNV exhibited strong heterogeneity across gene families and species, with contrasting evolutionary outcomes: A. thaliana showed greater retention of duplicated copies, whereas A. lyrata exhibited higher pseudogenization and turnover. CNV profiles were strongly structured geographically, reflecting known demographic and phylogeographic patterns in both species. Environmental association analyses revealed species-specific architectures: CNV in A. thaliana showed a diffuse, polygenic association with climate, whereas in A. lyrata associations were more strongly coupled to population structure. Despite the functional diversity of rapidly evolving families, environmentally associated CNVs were significantly enriched in defense- and stress-related functions. These results demonstrate that CNV-environment relationships emerge at the level of gene family networks and are shaped by genomic architecture and lineage history, highlighting CNV as a context-dependent driver of genome evolution and ecological differentiation. SummaryGene copy number variation--where individuals carry different numbers of copies of the same gene--is a potentially important but poorly understood source of genetic diversity. The authors studied how copy numbers evolve across four mustard family plant species and whether this variation helps plants adapt to different environments. They found that gene families involved in disease resistance and stress responses were especially prone to rapid copy number changes. These changes tracked geography and local climate, but in ways that differed between species depending on their evolutionary history. The findings highlight gene copy number variation as a key, underappreciated contributor to how plants adapt to their environments.

evolutionary biology↗

bioRxiv2024

SEGUID v2: Extending SEGUID checksums for circular, linear, single- and double-stranded biological sequences

BackgroundSynthetic biology involves combining different DNA fragments, each containing functional biological parts, to address specific problems. Fundamental gene-function research often requires cloning and propagating DNA fragments, such as those from the iGEM Parts Registry or Addgene, typically distributed as circular plasmids. Addgenes repository alone offers around 150,000 plasmids. To ensure data integrity, cryptographic checksums can be calculated for the sequences. Each sequence has a unique checksum, making checksums useful for validation and quick lookups of associated annotations. For example, the SEGUID checksum uniquely identifies protein sequences with a 27-character string. ObjectivesThe original SEGUID, while effective for protein sequences and single-stranded DNA (ssDNA), is not suitable for circular DNA since there is no natural starting position nor for double-stranded DNA (dsDNA) since two separate sequences are present. Challenges include how to uniquely represent linear dsDNA, circular ssDNA, and circular dsDNA. To meet these needs, we propose SEGUID v2, which extends the original SEGUID to handle additional types of sequences. ConclusionsSEGUID v2 produces orientation and rotation in-variant checksums for single-stranded, double-stranded, possibly staggered, linear, and circular DNA and RNA sequences. Customizable alphabets allow for other types of sequences. In contrast to the original SEGUID, which uses Base64, SEGUID v2 uses Base64url to encode the SHA-1 hash. This ensures SEGUID v2 checksums can be used as-is in filenames, regardless of platform, and in URLs, with minimal friction. AvailabilitySEGUID v2 is readily available for major program-ming languages, distributed under the MIT license. JavaScript package seguid is available on npm, Python package seguid on PyPi, R package seguid on CRAN, and a Tcl script on GitHub. These tools, along with documentation, examples, and an online SEGUID Calculator, can be found at https://www.seguid.org.

bioinformatics↗

bioRxiv2021

Insulin-dependent and -independent dynamics of insulin receptor trafficking in muscle cells

Insulin resistance contributes to type 2 diabetes and can be driven by hyperinsulinemia. Insulin receptor (INSR) internalization and cell-surface dynamics at rest and during insulin exposure are incompletely understood in muscle cells. Using surface labelling and live-cell imaging, we observed robust basal internalization of INSR in C2C12 myoblasts, without an effect of added insulin. Mass-spectrometry using INSR knockout cells as controls, identified high-confidence binding partners, including proteins associated with internalization. We confirmed known interactors, including IGF1R, but also identified underappreciated INSR-binding factors such as ANXA2. AlphaFold-Multimer analysis of these INSR-binding proteins predicted potential INSR binding sites of these proteins. Protein-protein interaction network mapping suggested links between INSR and caveolin-mediated endocytosis. INSR interacted with both caveolin and clathrin heavy chain (CLTC) in mouse skeletal muscle and C2C12 myoblasts. Whole cell 2D super-resolution imaging revealed that high levels of insulin (20 nM) increased INSR colocalization with CAV1 but decreased its colocalization with CLTC. Single particle tracking confirmed the colocalization of cell-surface INSR with both over-expressed CAV1-mRFP and CLTC-mRFP. INSR tracks that colocalized with CAV1 exhibited longer radii and lifetimes, regardless of insulin exposure, compared to non-colocalized tracks, whereas insulin further increased the lifetime of INSR/CLTC colocalized tracks. Overall, these data suggest that muscle cells utilize both CAV1 and CLTC-dependent pathways for INSR dynamics and internalization.

cell biology↗

bioRxiv2019

A 19-isolate reference-quality global pangenome for the fungal wheat pathogen Zymoseptoria tritici

BackgroundThe gene content of a species largely governs its ecological interactions and adaptive potential. A species is therefore defined by both core genes shared between all individuals and accessory genes segregating presence-absence variation. There is growing evidence that eukaryotes, similar to bacteria, show intra-specific variability in gene content. However, it remains largely unknown how functionally relevant such a pangenome structure is for eukaryotes and what mechanisms underlie the emergence of highly polymorphic genome structures. ResultsHere, we establish a reference-quality pangenome of a fungal pathogen of wheat based on 19 complete genomes from isolates sampled across six continents. Zymoseptoria tritici causes substantial worldwide losses to wheat production due to rapidly evolved tolerance to fungicides and evasion of host resistance. We performed transcriptome-assisted annotations of each genome to construct a global pangenome. Major chromosomal rearrangements are segregating within the species and underlie extensive gene presence-absence variation. Conserved orthogroups account for only [~]60% of the species pangenome. Investigating gene functions, we find that the accessory genome is enriched for pathogenesis-related functions and encodes genes involved in metabolite production, host tissue degradation and manipulation of the immune system. De novo transposon annotation of the 19 complete genomes shows that the highly diverse chromosomal structure is tightly associated with transposable elements content. Furthermore, transposable element expansions likely underlie recent genome expansions within the species. ConclusionsTaken together, our work establishes a highly complex eukaryotic pangenome providing an unprecedented toolbox to study how pangenome structure impacts crop-pathogen interactions.

genomics↗

bioRxiv2019

StormGraph: An automated graph-based algorithm for quantitative clustering analysis of single-molecule localization microscopy data

Clustering of proteins is crucial for many cellular processes and can be imaged at nanoscale resolution using single-molecule localization microscopy (SMLM). Ideally, molecular clustering in regions of interest (ROIs) from SMLM images would be assessed using computational methods that are robust to sample and experimental heterogeneity, account for uncertainties in localization data, can analyze both 2D and 3D data, and have practical computational requirements in terms of time and hardware. While analyzing surface protein clustering on B lymphocytes using SMLM, we encountered limitations with existing cluster analysis methods. This inspired us to develop StormGraph, an algorithm using graph theory and community detection to identify clusters in heterogeneous sets of 2D and 3D SMLM data while accounting for localization uncertainties. StormGraph generates both multi-level and single-level clusterings and can quantify cluster overlap for two-color SMLM data. Importantly, StormGraph automatically determines scale-dependent thresholds from the data using scale-independent input parameters. This makes identical choices of input parameter values suitable for disparate ROIs, eliminating the need to tune parameters for different ROIs in heterogeneous SMLM datasets. We show that StormGraph outperforms existing algorithms at analyzing heterogeneous sets of simulated SMLM ROIs where ground-truth clusters are known. Applying StormGraph to real SMLM data in 2D, we reveal that B-cell antigen receptors (BCRs) reside in a heterogeneous combination of small and large clusters following stimulation, which suggests for the first time that two conflicting models of BCR activation are not mutually exclusive. We also demonstrate application of StormGraph to real two-color and 3D SMLM data.

biophysics↗

bioRxiv2018

Arp2/3 complex-dependent spatial organization of the B cell receptor (BCR) impacts immune synapse formation, BCR signaling and B cell activation

When B cells encounter antigens on the surface of an antigen-presenting cell (APC), B cell receptors (BCRs) are gathered into microclusters that recruit signaling enzymes. These microclusters then move centripetally and coalesce into the central supramolecular activation cluster of an immune synapse. The mechanisms controlling BCR organization during immune synapse formation, and how this impacts BCR signaling, are not fully understood. We show that this coalescence of BCR microclusters depends on the actin-related protein 2/3 (Arp2/3) complex, which nucleates branched actin networks. Moreover, in murine B cells this dynamic spatial reorganization of BCR microclusters amplifies proximal BCR signaling reactions and enhances the ability of membrane-associated antigens to induce transcriptional responses and proliferation. Our finding that Arp2/3 complex activity is important for B cell responses to spatially-restricted membrane-bound antigens, but not for soluble antigens, highlights a critical role for Arp2/3 complex-dependent actin remodelling in B cell responses to APC-bound antigens.

immunology↗

bioRxiv2017

No evidence for avoidance of black rat scent by the presumably less competitive Natal multimammate mouse in a choice experiment

In Africa, indigenous multimammate mice (Mastomys natalensis) only appear to live commensally in houses when invasive black rats (Rattus rattus) are absent, yet little is known about the underlying mechanism. Avoidance through smell may cause the absence of M. natalensis from areas occupied by R. rattus, but this hypothesis has not yet been tested. We conducted a Y-maze choice experiment where 15 M. natalensis were offered a choice between corridors containing conspecific scent, R. rattus scent, and a control scent. Residence time in the R. rattus corridor was greater than that in the control corridor but equal to that in the M. natalensis corridor, suggesting that multimammate mice do not actively avoid the scent of their invasive competitor.

zoology↗