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Biology subjects

Olsen, S. C.

Publications and source records attributed to Olsen, S. C..

3 recordsLinked to original sources

Recurrent Duplication of the REST-NOA1 Locus Reveals a Hotspot of Regulatory Evolution Across Even-Toed Ungulates

Gene duplication is a major source of evolutionary novelty, yet recurrent duplication of the same genomic locus across independent lineages remains understudied. Using a chromosome-scale assembly and de novo annotation of the North American bison (Bison bison), we investigated the mechanisms underlying immune-system diversification in ungulates. Comparative genomics of bison, cattle, elk, and 13 mammalian species identified a large segmental duplication encompassing the regulatory genes REST and NOA1. Although similar duplications were present in 14/16 species examined, phylogenetic analyses revealed that duplicated genes cluster within species rather than across taxa, indicating repeated independent origins rather inheritance from a common ancestor. To characterize the evolutionary consequences of this duplication, we integrated transcriptomics from six tissues with weighted gene co-expression and comparative protein clustering. We identified extensive structural divergence among duplicated copies of REST and NOA1, including domain losses, truncations, and expression partitioning across tissues, consistent with functional divergence following duplication. Comparative analyses revealed substantial remodeling of immune-related genes in bison, including BOLA class I molecules, T-cell receptor genes, leukocyte immunoglobulin-like receptors, and regulators of immune signaling. These modifications included domain rearrangements, novel sequence insertions, and lineage-specific duplications associated with immune-related expression networks. Together, these findings identify the REST-NOA1 locus as a recurrent hotspot of segmental duplication in ungulates and demonstrate how repeated duplication, structural divergence, and regulatory partitioning contribute to genome evolution. These results suggest that immune system diversification in bison and related species has been shaped not only by sequence evolution but also by recurrent remodeling of regulatory pathways and antigen-recognition pathways.

bioinformatics↗

Temporal transcriptomic and microbial changes in American bison during experimental SARS-CoV-2 challenge

SARS-CoV-2 continues to pose a threat to humans as well as domestic and wild animals. The variability in severity of clinical signs, the zoonotic potential, and the host-specific response to infection contribute to the persistence of circulation of disease. In wildlife species white-tailed deer have been shown to be more permissive to infection than bovids. However, amongst bovids, American bison have shown a greater susceptibility than cattle. In this study we investigate the transcriptomic response to experimental SARS-CoV-2 infection in bison over time. Substantial numbers of differentially expressed genes were identified between pre- and 2, 5, 7, 14, and 21 days post-infection. KEGG and GO term analysis identified associations with immune response, inflammatory response, and viral infection including COVID-19. IPA analysis of the SARS coronavirus pathway highlighted differences in signaling at days 2 versus 21 post-infection. We additionally examined changes in the nasal microbiome of bison over the course of experimental infection, which suggested an increase in opportunity for secondary infection causing pathogens such as Mannheimia. Collectively this study presents a profile of bison transcriptomic response to SARS-CoV-2 infection and continues to expand our understanding of variation in host response. SummarySARS-CoV-2 remains a threat to humans, domestic animals, and wildlife. Among bovids, American bison show greater susceptibility than cattle. We characterized the bison transcriptomic response to experimental infection across six timepoints, identifying extensive differential gene expression associated with immune, inflammatory, and antiviral pathways. KEGG, GO, and IPA analyses revealed activation of coronavirus-related signaling and shifts between days 2 and 21. We additionally examined changes in the nasal microbiome of bison over the course of experimental infection, which suggested an increase in opportunity for secondary infection causing pathogens such as Mannheimia. The results refine understanding of host responses to SARS-CoV-2 in bison.

immunology↗

Quantification of Brucella abortus population structure in a natural host

Cattle are natural hosts of the intracellular pathogen, Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of approximately 106 uniquely barcoded B. abortus strains to temporally and spatially quantify population structure at the strain level during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a one-week timepoint. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached the parotid lymph nodes. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present one-week post infection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues. Significance statementUnderstanding microbial population dynamics during infection has important implications for disease management, transmission and pathogen evolution. A quantitative analysis of microbial population structure requires the ability to track individual strains. We used a pool of individually barcoded strains to measure changes in Brucella abortus population structure during infection of bovine hosts via the ocular conjunctiva, a natural route of entry. Cattle exert a severe bottleneck on the bacterial population entering through the conjunctival mucosa such that individual cells have a 0.0001 probability of colonizing a local draining lymph node. The populations in lymph nodes, even on different sides of the same animal, are distinct and dominated by a small number of highly abundant, spatially distinct clones.

microbiology↗