The epigenetic cost and benefit balance of giant virus endogenizations

Projektbeschreibung

Neue Einblicke in die Genomevolution

Manche Viren besitzen die Fähigkeit, ihr Genom dauerhaft in das des Wirts einzubetten. Dieser als Endogenisierung bezeichnete Prozess ist für kleine Viren gut dokumentiert. Bei Riesenviren, die Tausende von Genen tragen, wurde er bislang jedoch nicht eingehend erforscht. Zu verstehen, wie solche groß angelegten Integrationen zustande kommen, könnte wichtige Einblicke in die Genomevolution liefern. Das ERC-finanzierte Projekt ENDOGIANT untersucht, wie die DNS von Riesenviren in das Wirtsgenom integriert wird und wie die Chromatinregulierung diesen Prozess vermittelt. Anhand von Modellspezies aus entfernten Abstammungslinien werden die Forschenden untersuchen, wie diese Integrationen epigenetisch unterdrückt, potenziell für Immunität umgewidmet und über die tierischen Abstammungslinien weitergegeben werden. Insgesamt wird die Arbeit von ENDOGIANT ein neues Licht auf den Austauschmechanismus von genetischem Material zwischen Riesenviren und Eukaryoten werfen.

Ziel

Giant viruses, renowned for their exceptionally large genomes with thousands of genes, are increasingly being identified as integrated elements within eukaryotic genomes. This seemingly paradoxical process of endogenization is significant, as it represents a pathway for large-scale lateral gene transfer in eukaryotes. However, the initial integration of viral DNA can impose severe evolutionary costs, potentially being lethal for the host. The overarching hypothesis of this proposal is that the genetic conflict between giant virus and host genome merging is mediated at the chromatin regulation level.
Giant virus endogenizations are often epigenetically silenced and evolutionary dynamic. This rapid evolutionary pattern could imply benefits for the host. To test this, we will explore potential roles in immunity and gene family expansions.
Giant viruses, in turn, have their own set of chromatin regulation genes, which could be involved in hijacking host chromatin. To test this, we will characterise molecular interactions with host chromatin during infection and the role of captured eukaryotic transcriptional regulators encoded by giant virus.
Among eukaryotes, the animal kingdom is exceptional for its lack of reported giant virus endogenizations. However, our data reveal that all Hydra genomes contain giant virus integrations, hinting at an overlooked phenomenon. We will establish Hydra as a tractable model system for investigating the epigenetic regulation of these giant virus integrations in animals, and we will systematically survey giant virus endogenizations across diverse animal phyla.
Giant Viruses are ancient, having exchanged genetic material with eukaryotes since before the last common ancestor of modern eukaryotes to this day. Understanding the mechanisms and consequences of giant virus endogenization thus sheds light on an extraordinary and old source of genome innovation, and can illuminate the evolution of eukaryotic chromatin.