Biology subjects

Raj, M.

Publications and source records attributed to Raj, M..

4 recordsLinked to original sources

bioRxiv2026

Mating allows asexual female wasps to produce offspring both sexually and asexually, but their sexual daughters have reduced fecundity

Sexual reproduction is widespread despite being less efficient than asexual reproduction. While its long-term evolutionary benefits are well recognized, it remains unclear why facultative sex, which should allow lineages to balance the advantages of both sexual and asexual reproduction, is not more common. One potential reason is that intermittent sex imposes novel costs compared to obligate sex, limiting the persistence of facultatively sexual lineages and constraining introgression. We test this possibility using the sexually polymorphic aphid parasitoid wasp Lysiphlebus fabarum. We reared offspring from females who reproduced asexually or by facultative sex for three generations (without sex after the founding generation). We genotyped F1 females to confirm facultative sex and used antennomere number, a phenotypic marker associated with reproductive mode, to test whether mixed sexual-asexual genotypes could be tracked across generations. We found multiple barriers to facultative sex. Mating did not always result in offspring with sexual-asexual genotypes, and when sex did occur, broods were usually comprised of asexually and sexually produced offspring. Additionally, lineages founded by females produced through facultative sex showed reduced fecundity compared to asexually produced broods. We saw declining frequencies of the sexual antenna phenotype in the generations after facultative sex, suggesting that genotypes generated by facultative sex are selected against. Overall, our results provide empirical support for the idea that facultative sex can impose costs that persist beyond the initial sexual event. These costs, together with low realised rates of sex, may limit long-term introgression and explain why facultative sex appears rare compared to obligate sex.

evolutionary biology↗

bioRxiv2026

Mesoscale molecular architecture of the human striatum across cell types and lifespan

The human striatum is a central hub for a diverse array of motor, cognitive, and affective behaviors, yet it lacks obvious cytoarchitectural boundaries that define functional territories. Here, we uncover a robust and molecularly defined mesoscale architecture in the human striatum. Using Slide-tags, a scalable single-nucleus spatial transcriptomics technology, we profiled 1.1 million cells across the full span of the anterior striatum of 19 postmortem donors, spatially mapping all striatal populations. Our data uncover a natural subdivision of the striatum into six zones, each defined by molecularly distinct populations of medium spiny neurons, and featuring spatially coordinated neuron-astrocyte signaling. Relative to MSNs in ventral zones, MSNs in dorsal zones exhibit higher expression of genes for synaptic remodeling and plasticity via ephrin and TGF-beta, while the ventral zone is defined by greater expression of semaphorin, protein chaperone, and hedgehog signaling pathways. By imputing zonal identities onto a larger single-nucleus RNA-seq cohort of 131 donors, we find that the dorsal zones exhibit greater age-related transcriptional changes, and that overall, the gene-expression differences that define spatial zonation patterns are attenuated with advancing age. This atlas provides a mesoscale molecular definition of human striatal anatomy, linking cell type identity to functional specialization and aging susceptibility.

neuroscience↗

bioRxiv2023

The cell type composition of the adult mouse brain revealed by single cell and spatial genomics

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types, and their positions within individual anatomical structures, remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA-seq with Slide-seq-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain, and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signaling, elucidated region-specific specializations in activity-regulated gene expression, and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource (BrainCellData.org) should find diverse applications across neuroscience, including the construction of new genetic tools, and the prioritization of specific cell types and circuits in the study of brain diseases.

neuroscience↗

bioRxiv2022

Dynamic in vivo mapping of the methylproteome using a chemoenzymatic approach

Dynamic protein post-translation methylation is essential for cellular function, highlighted by the essential role of methylation in transcriptional regulation and its aberrant dysregulation in diseases including cancer. This underscores the importance of cataloging the cellular methylproteome. However, comprehensive analysis of the methylproteome remains elusive due to limitations in current enrichment and analysis pipelines. Here, we employ an L-Methionine analogue, ProSeMet, that is chemoenzymatically converted to the SAM analogue ProSeAM in cells and in vivo to tag proteins with a biorthogonal alkyne that can be directly detected via LC-MS/MS, or functionalized for subsequent selective enrichment and LC-MS/MS identification. Without enrichment, we identify lysine mono-, di-, and trimethylation, histidine methylation, and arginine methylation with site specific resolution on proteins including heat shock protein HSPA8, for which methylation is implicated in human disease. With enrichment, we identify 486 proteins known to be methylated and 221 proteins with novel methylation sites encompassing diverse cellular functions. Systemic ProSeMet delivery in mice pseudomethylates proteins across organ systems with blood-brain barrier penetrance and identifies site-specific pseudomethylation in vivo with LC-MS/MS. Leveraging these pipelines to define the cellular methylproteome may have broad applications for understanding the methylproteome in the context of disease.

biochemistry↗