Biology subjects

Olivera, B.

Publications and source records attributed to Olivera, B..

4 recordsLinked to original sources

bioRxiv2025

Molecular Characterization of Parabrachial Neurons in Xenopus laevis and Silurana tropicalis: Evolutionary Conservation and Sex-Specific Differences

Clawed frogs communicate acoustically to coordinate reproduction, with males producing species-specific advertisement calls to attract females. In Xenopus laevis, males generate fast trills composed of clicks repeated at 60 Hz, a feature absent in both Silurana tropicalis males and X. laevis females, whose calls consist of slower click rates (30 Hz and 7 Hz, respectively). In male X. laevis, fast trills are generated by premotor neurons in the parabrachial nucleus (PBN), known as Fast Trill Neurons (FTNs). We hypothesized that FTNs are unique in male X. laevis, and either absent or molecularly distinct in clawed frogs that do not produce fast trills. To test this, we used constellation pharmacology to profile receptor expression of neurons via intracellular Ca{superscript 2} responses to pharmacological agents in PBN neurons from male X. laevis, male S. tropicalis, and female X. laevis. Surprisingly, we found putative FTNs in all three groups, including those that do not produce fast trills. Furthermore, a similar proportion of FTNs across groups expressed fast-kinetic voltage-gated potassium channels known to support rapid firing, indicating that the presence of these channels does not correlate with the ability to produce fast trills. Instead, some of these channels were more prevalent in males of both species compared to female X. laevis, suggesting a potential sex-specific, non-vocal function. The discovery of FTNs with similar molecular profiles in non-fast-trilling individuals suggests that these neurons are conserved across species and sexes, and may serve other functions. In male X. laevis, FTNs may have been repurposed for fast trill production during speciation. These findings provide new insight into understanding how neural circuits evolve and diversify across species and sexes. Summary statementPremotor vocal neurons share molecular profiles across clawed frogs, despite differences in calls, revealing unexpected conservation and functional divergence of homologous neurons underlying evolution of vocal behavior.

neuroscience↗

bioRxiv2025

From Neuropeptides to Toxins: Illuminating the Origins of Venom Complexity in Cone Snails

New genes and gene functions are key drivers of evolutionary innovation. Venomous animals, such as cone snails, provide striking examples of gene innovation, yet the mechanisms by which toxins arise remain poorly understood. Using the Conus textile genome, we uncover how neuropeptide genes were recruited into the venom and neofunctionalized as doppelganger toxins. We identify over 20 independent recruitment events that evolved dynamically across the Conus lineage. Rather than arising from ohnologs of a whole-genome duplication event [~]100 mya, these toxins evolved through diverse mechanisms, including exon shuffling, alternative splicing, and ectopic recombination, often facilitated by lineage-specific transposable elements. Our findings reveal a dynamic interplay between genome architecture and molecular innovation, offering broad insight into the evolution of complex gene repertoires in venoms and beyond. One-Sentence SummaryDoppelganger toxins reveal how modular gene architecture, including 5UTR reuse and TE-driven recombination, fuels gene innovation in cone snails.

evolutionary biology↗

bioRxiv2025

Structural similarities reveal an expansive conotoxin family with a two-finger toxin fold

Venomous animals have evolved a diverse repertoire of toxins with considerable pharmaceutical potential. The rapid evolution of peptide toxins, such as the conotoxins produced by venomous marine cone snails, often complicates efforts to infer their evolutionary relationships based solely on sequence information. Structural bioinformatics, however, can provide robust support. Here, we first solve the NMR structure of a macro-conotoxin from the MLSML superfamily, Tx33.1, which is composed of 124 residues, including 12 cysteines. We then apply deep learning-based methods for structure prediction and comparison to identify structural similarities between this toxin and five additional, previously uncharacterized conotoxin superfamilies. Although only three of these superfamilies exhibit sequence homology, a combined approach incorporating structure prediction, structure comparison, and gene structure analysis supports the conclusion that all six superfamilies share a common evolutionary past. The Tx33.1 NMR structure displays similarity to the first two domains of Argos, a secretory protein from Drosophila melanogaster that comprises three domains, each harboring two short {beta}-stranded loops ("fingers"). Consequently, we propose the name "two-finger toxin (2FTX)" fold for this type of domain. Finally, using structure similarity searches, we identify a wide range of 2FTX proteins in protostomes, including non-venom-derived, secretory cone snail proteins. This study demonstrates how structural bioinformatics can be employed to uncover evolutionary relationships among rapidly evolving genes. It simultaneously identifies a large, previously unrecognized group of protostome 2FTX proteins, many of which exhibit close structural similarity to Argos and may perform a similar function in regulating EGFR signaling.

evolutionary biology↗

bioRxiv2022

Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins

Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, that defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and two additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of voltage-gated ion channels, Mu8.1 preferentially inhibited the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study demonstrates the feasibility of large, disulfide-rich venom-component investigation, an endeavor that will lead to the discovery of novel structures and functions in the previously underexplored group of macro-conotoxins.

biochemistry↗