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del Rosario, R. C. H.

Publications and source records attributed to del Rosario, R. C. H..

6 recordsLinked to original sources

Long-read transcriptomics highlights venom gland specialization and Inhibitor Cystine Knot (ICK) rich toxin diversity in Philippine tarantulas

Animal venoms are a rich source of bioactive molecules, yet their diversity remains incompletely characterized in many species. Here we present the first long-read transcriptomic analysis of venom glands from Philippine tarantulas (Theraphosidae), a highly endemic but understudied group. Using Oxford Nanopore sequencing, we reconstructed near full-length venom gland transcriptomes across multiple species and identified extensive repertoires of toxin-encoding peptides. Venom glands were enriched in cysteine-rich inhibitor cystine knot (ICK) peptides, which dominated the toxin landscape and are known modulators of ion channels. Cross-species comparative analyses revealed a distinct transcriptional signature separating venom from non-venom tissues, driven by coordinated expression of toxin-associated and regulatory gene families. Phylogenomic reconstruction based on orthologous peptides recovered expected taxonomic relationships while revealing potential lineage-specific diversification and potential cryptic taxa. Despite a conserved core set of toxin families, substantial variation in toxin composition was observed among species, consistent with rapid evolution driven by gene duplication and functional divergence. Analysis of highly expressed ICK peptides showed a conserved cysteine framework alongside marked sequence variability in inter-cysteine regions, supporting a model in which structural stability is maintained while functional diversification proceeds. Together, these findings establish the first long-read transcriptomic resource for Philippine theraphosid spiders, reveal a conserved molecular signature underlying venom gland specialization, and provide new insights into the diversification of ICK toxin repertoires that may facilitate future evolutionary and functional studies, including the discovery and characterization of bioactive venom peptides.

bioinformatics↗

Census and genetic analysis of the United States marmoset population

The common marmoset (Callithrix jacchus), a small monkey native to Brazil, has been used as a biomedical model in the United States (US) since the 1950s, yet the origins, genomic diversity, and population structure of current colonies remain poorly defined. Through the NIH Marmoset Coordinating Center, we registered and sampled most US research marmosets ([~]2,300 living animals) and assembled pedigrees and historical records for >10,000 individuals. We present a resource of >800 whole-genome sequences, largely from US colonies. These data reveal an unexpected population structure that predates the establishment of research colonies. Indeed, this population structure mirrors variation found in marmosets across Brazil. Leveraging sequenced families, we generate the first pedigree-based recombination map and improved estimates of de novo mutation processes for this species. Our insights into genetic diversity, structure, and inbreeding will guide colony management, inform disease modelling and strengthen the marmosets standing as a biomedical model. Further, this work demonstrates how coordinated efforts across colonies can enable a self-sustaining "living laboratory", supporting data sharing and well-powered studies beyond the reach of single institutions.

genetics↗

Genomic Insights into Derived Dwarfism and Exudivory in a Genus (Callithrix) of the World's Smallest Anthropoid Monkeys

The primate Callitrichidae family represents the smallest anthropoid primates, which are known to possess dietary specializations for eating viscous plant exudates (exudivory), and as callitrichids Callithrix marmosets push these biological traits to extremes. Using low-coverage whole genome sequencing of Callithrix species, we investigated Callithrix evolutionary history, species genetic diversity, and the genomic basis of derived small body size and exudivory. Our phylogenetic species tree shows that Callithrix likely originated in southeastern Brazil and migrated northward to the semi-arid regions of central and northeastern Brazil. We show that there is greater genetic similarity between smaller and more exudivorous Callithrix species relative to larger and less exudivorous species, and that the genus likely experienced extensive past reticulation. Based on these results, we argue that the Callithrix migration from the Atlantic Forest biome to the relatively more extreme environments of Cerrado/Caatinga biomes progressively reduced body size and increased exudivory specialization in Callithrix marmosets. We also identified species-specific candidate genes under putative positive selection for traits that include body growth, bone development, reproduction, fat metabolism, insulin signaling, and liporegulation. In conclusion, we increased genomic resources for understudied Callithrix species, while providing the most comprehensive overview of marmoset genomic diversity to-date, and identify several candidate genes under positive selection for traits related to small body size and exudivory. Future studies should sample wild marmosets more widely and perform higher-coverage genomic sequencing to better understand how specific genomic variants may impact the evolution of key Callithrix biological traits.

evolutionary biology↗

Sibling chimerism among microglia in marmosets

Chimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in which in utero connected circulatory systems (through which stem cells transit) lead to persistent blood chimerism (12-80%) throughout life. The presence of Y-chromosome DNA sequences in organs of female marmosets has long suggested that chimerism might also affect these organs. However, a longstanding question is whether this chimerism is driven by blood-derived cells or involves contributions from other cell types. To address this question, we analyzed single-cell RNA-seq data from blood, liver, kidney and many brain regions across a number of marmosets, using transcribed single nucleotide polymorphisms (SNPs) to identify cells with the siblings genome in various cell types within these tissues. Sibling-derived chimerism in all tissues arose entirely from cells of hematopoietic origin (i.e., myeloid and lymphoid lineages). In brain tissue this was reflected as sibling-derived chimerism among microglia (20-52%) and macrophages (18-64%) but not among other resident cell types (neurons, glia or ependymal cells). The percentage of microglia that were sibling-derived showed significant variation across brain regions, even within individual animals, likely reflecting distinct responses by genetic-sibling microglia to local recruitment or proliferation cues or, potentially, distinct clonal expansion histories in different brain areas. In the animals and tissues we analyzed, microglial gene expression profiles bore a much stronger relationship to local/host context than to sibling genetic differences. Naturally occurring marmoset chimerism will provide new ways to recognize the effects of genes, mutations and brain contexts on microglial biology and to distinguish between effects of microglia and other cell types on brain phenotypes.

neuroscience↗

Comparison of Mitogenomic and Mitochondrial Markers for the Phylogenetic and Evolutionary Study of Marmosets, with special focus on captive Callithrix jacchus

Marmosets, especially Callithrix jacchus, are becoming valuable, high-demand biomedical models but their supply outside of their native Brazil is limited. Thus, uncovering the ancestry and biogeographic origins of captive marmosets is an essential task to optimize their biomedical use. Such information facilitates assessing standing levels of captive marmoset genetic diversity, identifying hybrids, and maintaining genetic diversity of captive marmoset populations. Here, we present 16 newly sequenced mitochondrial genomes from marmosets with C. jacchus phenotypes from international biomedical and animal supply facilities. We combine these new data with publicly available sequences to compare usage of mitogenome and the mtDNA control region for determining the ancestry and diversity of captive marmosets. MtDNA control region and mitogenome haplotypes from all 16 newly sequenced marmosets grouped within C. jacchus phylogenetic clades. Overall, phylogenies based on mitogenomes rather than the control region showed better resolved branching patterns with stronger statistical support within C. jacchus clades. However, both mtDNA markers show that C. jacchus is the sister clade to the phylogenetic C. penicillata Caatinga biome clade. Callithrix jacchus mtDNA control region haplotypes showed the highest haplotype and nucleotide diversity, and were intermediate in terms of per sequence theta and polymorphic sites. The larger number of available Callithrix mtDNA control region sequences relative to mitogenomes was used to determine ancestral mtDNA haplotype biogeographic origins. However, biogeographic origins for many C. jacchus haplotypes including those from international captive facilities could not be determined, which we attributed to unknown provenance information from natural C. jacchus populations. Given our results, we encourage increased sampling and genomic sequencing efforts for natural C. jacchus populations in Brazil, and utilizing the mitogenome over other mtDNA markers for phylogenetic-based analyses. Further, combining marmoset mitogenomic data with phenotypic and nuclear genomic data will greatly enhance the biomedical use of marmosets.

genetics↗

Histone acetylome-wide association study of tuberculosis

Host-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro. We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

immunology↗