Since the discovery of giant viruses of the NucleoCytoplasmic Large DNA Viruses superfamily (NCLDV), several hypotheses have been suggested about their nature and origin, as well as about their relationship with Eukaryotes, triggering nearly as many controversies. Their many unexpected features that have been revealed so far have led several authors to suggest a possible role of ancient NCLDV-related viruses in the origin of modern eukaryotes. Notably, they could have been key-players in the formation of the nucleus, and may have provided new genes and/or chromosomes to proto-eukaryotes.
New NCLDV genomes are now regularly published, bringing more material to study these interactions: phylogenies of NCLDVs are nonetheless complex and prone to different interpretations. The phylogenetic analysis of DNA topoisomerase IB family (Topo IB) illustrates this complexity, with a short version in some NCLDVs, branching with Bacteria, and a long version in other NCLDVs, branching between Eukaryotes and Thaumarchaeota. The ancestral NCLDV Topo IB could either be the short version, possibly recruited from Bacteria before being replaced by the Topo IB from proto-eukaryotes in some NCLDVs, or the long version, with the short one replacing it in some NCLDVs.
Similarly, the two RNA polymerase large subunits are present in the three Domains of Life, but also in most NCLDVs (except Phycodnaviridae). The phylogenetic analyses of the concatenated alignments of the two protein sequences revealed that NCLDVs position is very sensitive to species sampling. These examples illustrate the difficulty to interpret the phylogenetic data obtained from NCLDVs informational proteins, and the need to have good markers. Nevertheless, the trees obtained also display patterns of distribution of NCLDVs, orientating further analyses of their core proteomes.