Gene duplication as a major force driving the genome expansion in some giant viruses

Abstract

ABSTRACT Giant viruses with their gigantic genomes are among the most intriguing components of the virosphere. How these viruses attained such giant genomes remains unclear, despite considerable efforts to understand this phenomenon. Here, we describe the discovery of cedratvirus pambiensis, an amoebal giant virus isolated in Brazil. Although the virion morphology and replication cycle of c. pambiensis are very similar to those described for other cedratviruses, whole genome sequencing revealed the largest cedratvirus genome ever described, with 623,564 base pairs and 842 predicted protein-coding genes (among them, 76 ORFans). Genome analysis has revealed an unprecedented number of paralogous genes, with ~73% of the c. pambiensis genome being composed of genes with two or more copies. Large families of functionally diverse paralogous genes included up to >70 copies and were distributed across the genome. The in-depth investigation of the mechanisms and origins of gene duplications revealed that both tandem-like duplications and distal transfer of syntenic blocks of genes contributed to the c. pambiensis genomic expansion. Finally, a comprehensive genome analysis of viruses from all known giant virus families suggested that gene duplication is one of the key mechanisms underlying genomic gigantism across the phylum Nucleocytoviricota . The expansion of viral genomes through successive duplications followed by subfunctionalization and exaptation of the paralogous gene copies may promote the adaptation of giant viruses to a variety of niches. IMPORTANCE Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes.