Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.02.13.705778

Calibrating and documenting host-switching and evolution of incompatibility loci for two closely related Wolbachia clades

Abstract

Maternally inherited Wolbachia alphaproteobacteria are the most common arthropod endosymbionts. Often Wolbachia spread to high frequencies through cytoplasmic incompatibility, in which cif loci act through sperm to kill embryos lacking Wolbachia. Closely related Wolbachia with diverse cif loci often associate with anciently diverged hosts, but the timescale of associations remains uncertain. We produce new calibrations based on filarial nematodes with vertically inherited Wolbachia that codiverge with their hosts. Applying these calibrations to Wolbachia variants closely related to pathogen-blocking wMel from Drosophila melanogaster, we demonstrate that over a timescale of 1-2 million years, a core set of single-copy Wolbachia loci evolve largely through bifurcation rather than by gene exchange with distant Wolbachia. Dating bifurcating core genomes, we show that "wMel-like" Wolbachia diverged 2.1x105-2.4x106 years inhabit dipteran and hymenopteran hosts diverged more than 108 years. Previous published analysis of variants related to wRi from D. simulans, the first Wolbachia found in a drosophilid, concluded that "wRi-like" Wolbachia spread among different Drosophila in tens of thousands of years. However, our new calibrations suggest these estimates from a mutation-based calibration underestimated wRi-like spread by about a factor of seven. In addition, cif exchanges between wMel-like and wRi-like Wolbachia genomes have occurred over [~]104-106 years. Comparing intact cif loci found in various Wolbachia, we find function-preserving selection in their evolution. We discuss these results in light of theoretical predictions concerning selection on cytoplasmic incompatibility phenotypes within and among host lineages. The wMel variants analyzed may offer new options for Wolbachia-based biocontrol efforts. Article SummaryMaternally transmitted Wolbachia endosymbionts associate with many arthropods. Closely related Wolbachia are known to occupy anciently diverged hosts, but the timescale of associations remains uncertain. Using genomic data from obligate Wolbachia codiverging with filarial nematodes, we calibrate Wolbachia molecular evolution. wMel-like variants that diverged about 104-106 years ago occur in hosts that diverged more than 108 years ago. Incompatibility loci move even more rapidly among these Wolbachia genomes. As these variants diverge, selection occurred on loci involved in both inducing and protecting against cytoplasmic incompatibility. These results elucidate Wolbachia host-range and genome dynamics and provide potential material for applications.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shropshire, J. D., Conner, W. R., Vanderpool, D., Hoffmann, A. A., Turelli, M., Cooper, B. S.. 2026-02-14. Calibrating and documenting host-switching and evolution of incompatibility loci for two closely related Wolbachia clades. https://doi.org/10.64898/2026.02.13.705778

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Prevalent Integration of both Xenotropic and Ecotropic Murine Leukemia Virus in the Human Genome of Xenografts

Humanized mouse models are widely used in medical research to represent human conditions (1, 2), but their fidelity could be compromised by mouse-originated infections. However, their susceptibility to mouse pathogens are rarely questioned (3). Here we screened 1,619 publicly available genomic sequencing runs from patient-derived xenograft (PDX) models for the integration of murine leukemia virus (MLV), a rodent retrovirus exists in the mouse genome as an endogenous retrovirus (4), within the human genome. We discovered substantial enrichment of human-MLV chimeric DNA in approximately 25% of them. Analyzing the human-MLV junctions, we found about 90% of them bearing the unmistakable hallmarks of retroviral integration, including the canonical MLV boundaries and the distinctive 4-bp target site duplications (5, 6). It was also assumed that mouse strains without the highly infectious Bxv1 provirus are safe from MLV contamination in xenografts (7, 8). However, we found many PDX models derived from Bxv1- strains, including the widely used NSG strain, are also contaminated by the supposedly rodent-specific ecotropic MLV (E-MLV). We further confirmed a complete E-MLV integrated into the human genome by both HiFi and sanger sequencing. Our discovery raises concerns that mouse-to-human retroviral transmission and integration is more common and less restrictive than previously appreciated. They support examination of MLV integration as a feature of humanized mouse models with implications on the fidelity of these models in recapitulating human cells and tissues. Our discovery also has underscored the importance of comprehensively inactivation of porcine endogenous retroviruses for the clinical application of xenotransplatation (9, 10).

microbiology↗

Necroptosis is a targetable driver of severe coronavirus pathogenesis

Human-pathogenic coronaviruses differ dramatically in pathogenicity but the underlying mechanisms are incompletely understood. Here, we demonstrate that highly pathogenic coronaviruses trigger necroptosis in the infected cells and lung tissues, whereas necroptosis is not detected in cells infected by seasonal coronavirus. Mechanistically, highly pathogenic coronaviruses produce Z-RNA, activate ZBP1 and initiates necroptotic cell death signaling, triggering necroinflammation and lung injury. In contrast, seasonal coronaviruses produce little to no Z-RNA, and do not activate necroptosis. Importantly, small-molecule inhibition of necroptosis attenuates inflammatory cytokine expression and markedly ameliorates lung damage in mice infected with all three highly pathogenic coronaviruses, independent of virus clearance. Overall, our study identifies necroptosis as a dominant mediator of coronavirus pathogenesis, and positions necroptosis blockade as a new therapeutic target against severe coronavirus diseases.

microbiology↗

POM121 regulates lentiviral nuclear import in a capsid-host factor-dependent manner

Lentiviruses such as human immunodeficiency virus 1 (HIV-1) access the nuclear lumen through the nuclear pore complex (NPC), a process coordinated by the interactions between the viral capsid and nucleoporins (NUPs). Here, using unbiased proteomic screens, we identified several capsid-associated NUPs, including POM121. Depletion of POM121 impaired HIV-1 infection in multiple cell lines and in primary CD4+ T cells, whereas equine infectious anaemia virus (EIAV) infection was enhanced, indicating that POM121 effect is virus-specific. A cytoplasmic carboxy-terminal fragment of POM121, containing its FG-rich region inhibited HIV-1 and a broader range of lentiviruses. Analysis of HIV-1 capsid mutants showed that physical interaction with POM121 does not predict functional dependence, as capsids retaining POM121 binding remained insensitive to its depletion. Strikingly, loss of cyclophilin A (CypA) completely abolished HIV-1 dependence on POM121, whereas depletion of CPSF6 produced only partial rescue, demonstrating that POM121 sensitivity is dictated by the broader network of capsid-host interactions. Finally, POM121 depletion impaired HIV-1 nuclear accumulation and selectively disrupted the nuclear import of other viral and cellular cargo. Together, these findings identify POM121 as a selective regulator of lentiviral nuclear entry whose functional contribution is determined by capsid and host-factor context.

microbiology↗