Biology subjects

Alvarado, P.

Publications and source records attributed to Alvarado, P..

3 recordsLinked to original sources

bioRxiv2025

Telomeric assemblies of Paracoccidioides genomes

Paracoccidioides is a genus of dimorphic fungal pathogens endemic to Latin America. We generated long-read de novo assemblies for 11 isolates representing four species of the brasiliensis complex (P. brasiliensis, P. americana, P. restrepiensis, P. venezuelensis) and P. lutzii. These include the first complete telomere-to-telomere assemblies for P. brasiliensis (Pb18) and P. americana (Pb03), each with five chromosomes. Comparative analyses revealed chromosomal fusion and fission events distinguishing P. brasiliensis and P. americana, and a 90 kb tandem duplication in P. americana containing siderophore biosynthesis genes (sid1, sid3, sid4), a cluster of putative virulence factors. Mitochondrial genomes showed conserved gene order but a phylogenetic topology inconsistent with the nuclear tree, suggesting mitochondrial introgression between P. lutzii and P. venezuelensis. RNA transposable elements were enriched near telomeres, correlated with genome size, and most abundant in P. lutzii. These assemblies provide key resources for understanding genome evolution and introgression in Paracoccidioides. SIGNIFICANCESpecies of Paracoccidioides cause paracoccidioidomycosis, a systemic mycosis that remains a major public health problem in Latin America. Despite their clinical importance, genome evolution across the genus is poorly understood owing to the lack of complete reference assemblies. Here, we present the first telomere-to-telomere reference genomes for P. brasiliensis and P. americana, enabling a comprehensive comparison of chromosomal structure across the genus. Our analyses reveal that the nuclear genome is highly dynamic and shaped by large-scale rearrangements and structural variants, including the duplication of a siderophore biosynthesis-related gene cluster linked to virulence. In contrast, the mitochondrial genome is structurally conserved but shows introgression between species, revealing hidden evolutionary exchange. Together, these genomic resources redefine our understanding of Paracoccidioides evolution and provide a foundation for advances in molecular diagnostics, epidemiological surveillance, and studies of fungal pathogenicity.

microbiology↗

bioRxiv2025

Zebrafish armc9 mutant reveals a link between ARM-Type fold domain loss, inflammation, and spinal curvature

The vertebral column (VC) defines the central axis of vertebrates. Among its malformations, adolescent idiopathic scoliosis (AIS) is the most common, characterized by lateral spine curvature without congenital abnormalities. While its etiology remains elusive, genetic studies in zebrafish have linked AIS to skeletogenesis, cilia structure, cerebrospinal fluid flow, and inflammation. In this study, we characterized the zebrafish armc9 mutant, exhibiting AIS-like curvature without vertebral malformations, subcommissural organ, or Reissner fiber structure disruptions. We also detected an inflammatory response at the curvature origin. Structural bioinformatics and molecular docking analyses suggest that the mutant Armc9 protein partially lacks the functional ARM-type fold domain, which is crucial for its interaction with Togaram1, revealing that both proteins are relevant for ciliary signaling and spine curvature. Phylogenetic analyses indicate that the ARMC gene family encompasses 12 members, highlighting that the Armc9 gene has deep evolutionary roots. Our results demonstrate that the zebrafish armc9 mutant accurately represents the AIS phenotype, suggesting that the loss of Armc9s C-terminal ARM-type fold domain could affect the ciliary integrity and contribute to spine curvature by altering the skeletogenic environment. Taken together, this study proposes that the zebrafish armc9 mutant offers a unique opportunity to understand the etiology of AIS and provides new insights into the molecular interaction networks of Armc9 in ciliary signaling.

developmental biology↗

bioRxiv2019

Strong population structure in Venezuelan populations of Coccidioides posadasii

Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in Arizona (AZ), Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. As expected, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck, and shows strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.

evolutionary biology↗