Wright, S. L. | Search bioRxiv

bioRxiv2026

The Dynamics of Long Terminal Repeat Proliferation in the Hesperis matronalis Genome

Genome sizes vary across four orders of magnitude in flowering plants, with consequences for evolution. Much of this variation is due to differences in transposable element content, particularly in long terminal repeat (LTR) retrotransposons. Despite their importance in plant genome evolution, LTRs have long been challenging to characterize because of their repetitive nature, but recent advances in sequencing allow more detailed explorations of their behavior. They are now known to occupy distinct genomic niches, and to evolve and proliferate over time as they escape host controls. In this study, we present a new genome sequence of the largest Brassicaceae genome, Hesperis matronalis, and describe its transposable element complement and how LTRs contributed to its genome expansion. We find evidence for both early proliferation of Ty3 elements and rapid recent expansion of Ty1-copia elements. In addition, we place the H. matronalis LTRs in a broader context of LTR evolution in the Brassicaceae, showing that the dominant copia families are part of an evolutionary radiation endemic to Hesperis. Finally, we describe differences in LTR age, proximity to genes, and apparent removal rate which suggest consistent genomic niches over the lifespan of a TE family. These results shed light on how LTRs evolve dynamically with host genomes, and have contributed to the expansion of the largest genome in the Brassicaceae. Significance StatementOrganisms differ in many ways, including the size of their genomes. Genome size, in turn, can affect many aspects of evolution, such as what kinds of mutations are available to natural selection and how effectively natural selection can act. The "complexity" of an organism does not predict its genome size; rather, much of this variation is explained by the amount of transposable elements, or "jumping genes," that inhabit a genome. This study describes the evolutionary history of the transposable elements in dames rocket (Hesperis matronalis), which has the largest genome of any plant in the mustard family (Brassicaceae). We find that the genome inflation in Hesperis is due to transposable elements that are not found elsewhere in the Brassicaceae, and likely diversified within Hesperis. Characterizing the evolution and behavior of transposable elements in this genome offers a better understanding of the forces that determine genome size and ultimately affect the evolution of life on earth.

genomics↗

bioRxiv2020

Chlorotoxin Redirects Chimeric Antigen Receptor T Cells for Specific and Effective Targeting of Glioblastoma

While chimeric antigen receptor (CAR) T cells have demonstrated antitumor activity against glioblastoma (GBM), tumor heterogeneity remains a critical challenge. To more effectively target heterogeneous GBMs, we report the development of a novel peptide-based CAR exploiting the GBM-binding potential of chlorotoxin (CLTX). CLTX bound a greater proportion of tumor cells than GBM-associated antigens EGFR, HER2 and IL13R2. CAR T cells bearing CLTX as the targeting domain (CLTX-CAR), mediated potent in vitro and in vivo anti-GBM activity, and efficiently targeted tumors lacking expression of other GBM-associated antigens. Importantly, CLTX-CAR T cells exhibited no observable off-target effector activity against normal cells, or when adoptively transferred into mice. Effective targeting by CLTX-CAR T cells required cell surface expression of matrix metalloproteinase-2 (MMP-2). Our results are the first demonstration of a peptide toxin utilized as a CAR targeting domain, expanding the repertoire of tumor-selective CAR T cells with the potential to reduce antigen escape. One Sentence SummaryChimeric antigen receptors incorporating chlorotoxin as the tumor targeting domain recognize and kill glioblastoma with high specificity and potency.

immunology↗