Evolution of ubiquitin, cytoskeleton, and vesicular trafficking machinery in giant viruses.

Abstract

Members of the phylum Nucleocytoviricota, which include "giant viruses" known for their large physical dimensions and genome lengths, are a diverse group of dsDNA viruses that infect a wide range of eukaryotic hosts. The genomes of nucleocytoviruses frequently encode eukaryotic signature proteins (ESPs) such as RNA- and DNA-processing proteins, vesicular trafficking factors, cytoskeletal components, and proteins involved in ubiquitin signaling. Despite the prevalence of these genes in many nucleocytoviruses, the timing and number of gene acquisitions remains unclear. While the presence of DNA- and RNA-processing proteins in nucleocytoviruses likely reflects ancient gene transfers, the origins and evolutionary history of other proteins are largely unknown. In this study, we examined the distribution and evolutionary history of a subset of viral-encoded ESPs (vESPs) that are widespread in nucleocytoviruses. Our results demonstrate that most vESPs involved in vesicular trafficking were acquired multiple times independently by nucleocytoviruses at different time points after the emergence of the eukaryotic supergroups, while viral proteins associated with cytoskeletal and ubiquitin system proteins exhibited a more complex evolutionary pattern exhibited by both shallow and deep branching viral clades. This pattern reveals a dynamic interplay between the co-evoluton of eukaryotes and their viruses, suggesting that the viral acquisition of many genes involved in cellular processes has occurred both through ancient and more recent horizontal gene transfers. The timing and frequency of these gene acquisitions may provide insight into their role and functional significance during viral infection.IMPORTANCEThis research is pertinent for understanding the evolution of nucleocytoviruses and their interactions with eukaryotic hosts. By investigating the distribution and evolutionary history of viral-encoded eukaryotic signature proteins, the study reveals gene transfer patterns, highlighting how viruses acquire genes that allow them to manipulate host cellular processes. Identifying the timing and frequency of gene acquisitions related to essential cellular functions provides insights into their roles during viral infections. This work expands our understanding of viral diversity and adaptability, contributing valuable knowledge to virology and evolutionary biology, while offering new perspectives on the relationship between viruses and their hosts.