The GC% landscape of the Nucleocytoviricota

Genomic studies on sequence composition employ various approaches, such as calculating the proportion of guanine and cytosine within a given sequence (GC% content), which can shed light on various aspects of the organism’s biology. In this context, GC% can provide insights into virus-host relationships and evolution. Here, we present a comprehensive gene-by-gene analysis of 61 representatives belonging to the phylum Nucleocytoviricota, which comprises viruses with the largest genomes known in the virosphere. Parameters were evaluated not only based on the average GC% of a given viral species compared to the entire phylum but also considering gene position and phylogenetic history. Our results reveal that while some families exhibit similar GC% among their representatives (e.g., Marseilleviridae), others such as Poxviridae, Phycodnaviridae, and Mimiviridae have members with discrepant GC% values, likely reflecting adaptation to specific biological cycles and hosts. Interestingly, certain genes located at terminal regions or within specific genomic clusters show GC% values distinct from the average, suggesting recent acquisition or unique evolutionary pressures. Horizontal gene transfer and the presence of potential paralogs were also assessed in genes with the most discrepant GC% values, indicating multiple evolutionary histories. Taken together, to the best of our knowledge, this study represents the first global and gene-by-gene analysis of GC% distribution and profiles within genomes of Nucleocytoviricota members, highlighting their diversity and identifying potential new targets for future studies.