Rise of the viral giants: common themes underlying genome gigantism in eukaryotic viruses and bacteriophages

Recent research has shown that the biosphere harbors an immense diversity of large and complex DNA viruses that infect a wide range of hosts. This is best exemplified by giant viruses of eukaryotes (phylum Nucleocytoviricota ) and large phages, also referred to as jumbo phages, that infect bacteria (class Caudoviricetes ). Both groups independently evolved large genomes and complex infection strategies, and recent research reveals striking convergences between these viral groups despite their distinct evolutionary origins. Virus factories and phage nuclei separate transcription from translation, mediate spatiotemporal regulation of infection, and involve elaborate interactions with host cytoskeletal systems. Moreover, both viral groups harbor an expanded repertoire of genes acquired from cellular hosts, including transcription and translation-related genes and metabolic enzymes, suggesting convergent strategies to optimize host takeover. Additionally, both lineages are embedded in networks of hyperparasitic interactions, including viral parasites and phage satellites, as well as other selfish genetic elements such as transposons and homing endonucleases, which may, in some cases, facilitate genome innovation and provide fitness benefits. The repeated emergence of genome gigantism across diverse viral clades within both the Nucleocytoviricota and Caudoviricetes suggests that selective pressures favoring gene gain, potentially through a genomic accordion mechanism, are widespread. Yet, genome expansions also harbor many features that are lineage-specific and highly context-dependent. This review explores the mechanistic, functional, and evolutionary parallels that shape the biology of genome gigantism in the virosphere. • Viruses with large DNA genomes have arisen multiple times independently. • They have evolved similar infection strategies, such as viral ‘organelles’ for replication. • They encode diverse cellular genes to hijack the host cell. • Despite convergence, several lineages have unique evolutionary trajectories. • There are likely multiple drivers of genome gigantism in the virosphere.