Biology subjects

Verbakel, L.

Publications and source records attributed to Verbakel, L..

3 recordsLinked to original sources

bioRxiv2026

MOSAIC: a longitudinal phenotypic clock to dissect organismal aging trajectories in C. elegans

Interventions that extend lifespan do not necessarily preserve healthspan, the portion of life spent in good health. This disconnect has intensified interest in biological aging clocks as quantitative proxies of organismal health. However, most existing clocks rely on invasive or endpoint measurements, providing static estimates that capture biological age at a single time point and offer limited insight into aging trajectories - the dynamic patterns through which physiological resilience and functional capacity change within individuals over time. Here we combine standardized, high-frequency imaging of individual Caenorhabditis elegans across the lifespan with machine learning to develop MOSAIC (Modular Organismal Signature of Aging In C. elegans), a non-invasive phenotypic clock that estimates biological age longitudinally at single-organism resolution. Leveraging [~]3750 animals, [~]230000 observations and 29 phenotypic features, MOSAIC predicts biological age with high accuracy and resolves organism-wide aging trajectories at high temporal resolution. Beyond age prediction, MOSAIC decomposes biological age into contributions from distinct physiological modules, enabling mechanistic interpretation of organismal decline. Applying MOSAIC to natural lifespan variation, dietary restriction, longevity mutants and pharmacological interventions reveals that lifespan extension can emerge through distinct, time-dependent phenotypic trajectories rather than a uniform slowing of aging. Interventions with similar effects on longevity produce divergent biological-age trajectories and distinct combinations of younger and older traits, highlighting context-dependent physiological trade-offs. MOSAIC provides a scalable, non-invasive framework to repeatedly quantify biological age across the lifespan and to compare interventions based on how they reshape aging trajectories.

bioinformatics↗

bioRxiv2026

Abdominal-B regulates the male seminal fluid transferome and new female fecundity factors required for sperm sex peptide binding

Seminal fluid proteins determine reproductive success in a wide range of animals. In the Drosophila male accessory gland, seminal fluid is mainly produced by two cell types, a vast majority of main cells and a small number of secondary cells that possess a specialized secretory apparatus with unusually enlarged dense core granule vesicles. Loss of Abdominal-B expression from secondary cells in the enhancer mutant iab-6cocu disrupts their transcriptional and secretory identity. Consequently, mutant males fail to induce the long-term post-mating response in females, which is characterized by a loss of receptivity and sustained egg laying. Here, we determine how secondary cells shape the seminal transferome and the female response by assessing iab-6cocu male accessory gland and female mate reproductive tract proteomes. We find downregulation of seminal fluid proteins that constitute a signaling network that enables sperm binding and the sustained action of the key regulator Sex peptide and identify two new Sex peptide network proteins crucial for female fecundity, Cornutus (CG1701) and Hanrej (CG42564). Cornutus is required for mating dependent dense core granule vesicle release, providing a link between the products of these compartments and the female long-term post-mating response. Our data highlights the importance of secondary cell signaling and secretion for overall seminal fluid composition and Sex peptide network function as well as the interdependence of main and secondary cells and their secretory products, advancing the general understanding of how seminal fluid signaling pathways modulate female physiology, sperm use and offspring production.

physiology↗

bioRxiv2025

Correlated Gene Copy Number Changes in a Seminal Fluid Protein Network in Drosophila

Reproductive proteins often diverge rapidly between species, yet network function must be maintained. Shared selective pressures on network members and compensatory changes between members can drive their parallel evolutionary trajectories. Indeed, correlated evolutionary rates of amino acid sequence change have been observed for interacting reproductive proteins. But whether gene copy number changes also correlate has not been widely studied. Here, we investigated copy number variation (CNV) of genes in the Drosophila Sex Peptide Seminal Fluid Protein (Sfp) network. Previous research analyzed CNV of the Sfp Sex Peptide (SP) in Drosophila species. We focus on 9 other Sfps whose function is required to mediate the binding of SP to sperm in D. melanogaster which is required for persistence of female post-mating responses. To exhaustively annotate CNV of genes, we developed a computational pipeline pairing iterative protein queries to genome sequence searches with phylogenetic clustering to resolve homology relationships. We observed that the Sfp networks genes are ancestral to Drosophila and that there were repeated duplications and losses of network members across the genus. We detect statistically significant correlations in gene duplication or loss events among network proteins, and show this can be used to identify new members of the network. We also investigated CNV of female-derived proteins that act downstream of the SP sperm-binding network to modulate SP function, these proteins showed no significant correlation of gene turnover events with SP or its network. Our results provide insight into how evolving reproductive genes tolerate duplication and loss, and how network relationships could constrain reproductive protein evolution. Significance StatementReproductive proteins often diverge rapidly between species, yet network function must be maintained. Shared selective pressures on network members and compensatory changes between members can drive their parallel evolutionary trajectories. We report correlated gene duplication and loss among members of the Drosophila Sex Peptide seminal fluid protein network, suggesting that duplication or loss events may drive corresponding events in other network genes. This work is a natural extension of the idea of evolutionary rate covariation, but instead of scoring rates of substitution it tracks correlated duplication and loss events on the phylogeny. Applied to the Sex Peptide network, the method reveals striking patterns, especially for coordinated loss, and identifies a new network gene that is experimentally confirmed.

evolutionary biology↗