[R35] Determinants of intra- and inter-genomic mobility in eukaryotic genomes

Ente: National Institute of General Medical Sciences

Scadenza: 2031-04-30

Importo max: $471,625

Paese: US

Descrizione

PROJECT SUMMARY Transposable elements (TEs) constitute a ubiquitous, and often predominant, component of virtually every eukaryotic genome, exerting a profound impact on genome structure, function, and evolution. Horizontal gene transfer (HGT) represents another source of novel genetic material, the importance of which is well- documented in bacteria, but is still controversial in eukaryotes, especially metazoans. Our lab has pioneered the studies of HGT as the source of evolutionary innovation in eukaryotes, by discovering massive HGT in genomes of bdelloid rotifers, in which 8-10% of all coding sequences originate from non-metazoan sources. Recently, we discovered that HGT was responsible for recruitment of N4-methycytosine, a DNA modification previously seen only in bacteria, into the eukaryotic chromatin-based epigenetic system for TE suppression, via fusion of a bacterial N4C-methyltransferase to a eukaryotic chromodomain. Further discoveries related to HGT-mediated innovation included recruitment of bacterial non-ribosomal peptide synthetases to deploy antibiotic-like secondary metabolites against deadly fungal infections. Moreover, we found that horizontally transferred reverse transcriptases, which normally ensure TE retrotransposition, have been domesticated in numerous fungal and invertebrate species to perform a specific function in environmental stress response. Here, we seek to capitalize on our findings and build an integrated picture of the eukaryotic mobilome in a broader sense, from under-explored TE types to the newly acquired genes of foreign origin. We will focus on elucidating the hitherto unknown mechanisms of transposition of intron-containing retroelements, which challenge the existing paradigm of intron elimination following a retrotransposition cycle, and of virus-like elements, which may have the capacity to penetrate host membranes for cell-to-cell transmission. Moreover, we argue that such TEs may undergo and facilitate inter-genomic mobility in as yet unexplored ways, as implied by their structural features, coding capacity, and cargo-bearing properties. These studies aim to close the final remaining gaps in our knowledge of eukaryotic TE transposition mechanisms. We seek to uncover the fundamental principles that determine the potential for intra- and inter-genomic movement of mobile DNA segments in eukaryotes, and may serve to improve TE-based strategies for genome editing and engineering. Istituzione: MARINE BIOLOGICAL LABORATORY PI: Irina Arkhipova Progetto: 1R35GM163697-01

Settori: National Institute of General Medical Sciences

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