Biology subjects

Gonzales, C. A.

Publications and source records attributed to Gonzales, C. A..

3 recordsLinked to original sources

bioRxiv2026

Population genomics of Drosophila pseudoobscura

Drosophila pseudoobscura is an historically important organism in evolutionary genetics, serving as a model system in studies of chromosomal inversions, speciation, sex chromosome evolution, and sex-ratio drive. However, previous population genetics analysis of D. pseudoobscura focused on individual chromosomes or used fragmented genome assemblies as a reference. To address these shortcomings, we generated a D. pseudoobscura population genomics resource consisting of newly sequenced genomes from 60 inbred lines sampled across the species geographic range in North America. Using these data and a chromosome-scale reference genome, we examined patterns of nucleotide diversity and population structure across the chromosomes. We found no strong evidence of population structure on most chromosomes, consistent with prior results. In contrast, we identified population structure on the third chromosome, which we attributed to a well-characterized inversion polymorphism. We assigned individual third chromosome haplotypes to inversion arrangements, demonstrating how tests for population structure can be used to identify polymorphic chromosomal rearrangements. Tajimas D was negative across most of the genome, consistent with a recent population expansion. However, the distribution of genetic variation differed across third chromosome inversion arrangements in ways that were consistent with their hypothesized evolutionary histories, and we identified inter-arrangement genetic differentiation that could be attributed to the inversions suppressing genetic exchange. The population genomic data we have collected is publicly available and will support future research on evolutionary genetics. SummaryThe genomes of 60 isolates of Drosophila pseudoobscura were sequenced and analyzed. This species is a model organism for multiple areas in evolutionary genetics research, including chromosomal rearrangement, sex chromosomes, and speciation. This article presents the largest population genomic data set collected in this species. The analysis of the data demonstrates how population structure detection approaches can be used to identify polymorphic chromosomal inversions. The data presented will be valuable for future work on fundamental questions in population genetics.

genomics↗

bioRxiv2025

Monkeypox Virus Clade IIb Isolate Exhibits Reduced Virulence Relative to Clade IIa Isolates in Multiple Murine Models

Monkeypox virus (MPXV) is the causative agent of mpox disease in humans. The virus is comprised of two clades, Central African clade I and West African clade II with case fatality rates of [~]11 and [~]4%, respectively. Since the discovery of mpox disease in 1970, the virus has been restricted to Africa. However, in 2022, a previously unrecognized subclade IIb caused the largest global outbreak of mpox disease with a case fatality rate of [~]0.2%. The difference in virulence of MPXV subclades in human infection warrants further investigation, however, one critical limitation is the lack of susceptible small animal models. In this study, we investigated the susceptibility of four murine models, including CAST-EiJ and three immunocompromised models (C57BL/6 Ifnar-/-, C57BL/6 Ifngr-/-, and C57BL/6 Ifnar-/-/Ifngr-/-) to MPXV clade IIa (WR 7-61 and US-2003) and IIb (MA-2022) isolates. All four mouse models were susceptible to clade IIa infection, leading to severe disease marked by decreased body temperature, weight loss, and lethality. In contrast, clade IIb infection produced minimal to mild disease at similar doses in all four murine models. The clade IIb isolate produced severe disease (40% lethality) at only the highest dose (8.0 log10 PFU) in the most susceptible immunocompromised mouse model, C57BL/6 Ifnar-/-/Ifngr-/-. This is the first demonstration of lethal disease with clade IIb in a murine model. In addition, these data demonstrate that clade IIa is [~]100- to 100,000-fold more virulent than clade IIb and provide three additional murine models for investigating MPXV infection and pathogenesis. IMPORTANCEMpox is an emerging human disease caused by four distinct MPXV subclades (Ia, Ib, IIa, and IIb). Despite genetic similarities, the case fatality rate varies considerably between the subclades: Ia ([~]11%), Ib and IIa ([~]4%), and IIb ([~]0.2%). Since 2022, multiple mpox outbreaks have occurred due to previously unrecognized subclades, leading to the declaration of two public health emergencies by the World Health Organization. This unprecedented global spread, coupled with the variation in severity of human disease, underscores the importance of research into the pathogenesis of emerging MPXV subclades. However, a critical limitation is the lack of suitable small animal models. This study identifies three additional murine models susceptible to MPXV clade II infection and demonstrates significant virulence differences between clade IIa and IIb. These models will enable rapid characterization of previously unrecognized subclades and will facilitate countermeasure development.

microbiology↗

bioRxiv2024

Testis- and ovary-expressed polo transcripts and gene duplications affect male fertility when expressed in the germline

Polo-like kinases (Plks) are essential for spindle attachment to the kinetochore during prophase and the subsequent dissociation after anaphase in both mitosis and meiosis. There are structural differences in the spindle apparatus between mitosis, male meiosis, and female meiosis. It is therefore possible that alleles of Plk genes could improve kinetochore attachment or dissociation in spermatogenesis or oogenesis, but not both. These opposing effects could result in sexually antagonistic selection at Plk loci. In addition, Plk genes have been independently duplicated in many different evolutionary lineages within animals. This raises the possibility that Plk gene duplication may resolve sexual conflicts over mitotic and meiotic functions. We investigated this hypothesis by comparing the evolution, gene expression, and functional effects of the single Plk gene in Drosophila melanogaster (polo) and the duplicated Plks in Drosophila pseudoobscura (Dpse-polo and Dpse-polo-dup1). We found that the protein-coding sequence of Dpse-polo-dup1 is evolving significantly faster than a canonical polo gene across all functional domains, yet the essential structure of encoded protein appears to be retained. Dpse-polo-dup1 is expressed primarily in testis, while other polo genes have broader expression profiles. Furthermore, over or ectopic expression of polo or Dpse-polo in the D. melanogaster male germline results in greater male infertility than ectopic expression of Dpse-polo-dup1. Lastly, ectopic expression of Dpse-polo or an ovary-derived transcript of polo in the male germline causes males to sire female-biased broods. However, there is no sex-bias in the progeny when Dpse-polo-dup1 is ectopically expressed or a testis-derived transcript of polo is overexpressed in the D. melanogaster male germline. Our results therefore suggest that Dpse-polo-dup1 may have experienced positive selection to improve its regulation of the male meiotic spindle, resolving sexual conflict over meiotic Plk functions. Alternatively, Dpse-polo-dup1 may encode a hypomorphic Plk that has reduced deleterious effects when overexpressed in the male germline. Similarly, testis transcripts of D. melanogaster polo may be optimized for regulating the male meiotic spindle, and we provide evidence that the untranslated regions of the polo transcript may be involved in sex-specific germline functions.

genetics↗