The epigenetic cost and benefit balance of giant virus endogenizations

Descripción del proyecto

Nuevos conocimientos sobre la evolución del genoma

Algunos virus pueden integrar de forma permanente su genoma en el del hospedador. Este proceso de endogenización está bien documentado en los virus pequeños. Sin embargo, no se ha estudiado lo suficiente en los virus gigantes, que portan miles de genes. Comprender cómo se produce este proceso en los virus gigantes podría contribuir a esclarecer la evolución del genoma. En el proyecto ENDOGIANT, financiado por el Consejo Europeo de Investigación, se estudiará cómo se integra el ADN de los virus en el genoma hospedador y de qué manera la regulación de la cromatina interviene en ese proceso. Los investigadores utilizarán especies modelo de linajes distantes para analizar cómo estas integraciones quedan silenciadas mediante mecanismos epigenéticos, cómo pueden reutilizarse en funciones de defensa inmunitaria y cómo se han distribuido a lo largo de distintos linajes animales. En conjunto, la investigación de ENDOGIANT proporcionará nuevos conocimientos sobre el mecanismo de intercambio de material genético entre virus gigantes y eucariotas.

Objetivo

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.