Giant viruses: spore‐like missing links between Rickettsia and mitochondria?

Phyloproteomics indicate common viral origin from ancient cells before archaea, bacteria, and eukaryota split and subsequent size and complexity reductions occurred. Further independent evidence for the cellular origin of viruses is reviewed for the virus order Megavirales , focusing on the family Poxviridae . Megavirales comprises giant viruses, double‐stranded DNA viruses whose genomes exceed some bacterial ones and large enough to parasitize large‐celled protists (amoeba). Giant viruses, virophages, and mitochondria have homologous DNA and RNA polymerases and share RNA splicing punctuation by stem–loop hairpins. Giant virus factories and amoeban mitochondria colocate, with viral proteins homologous to mitochondrial proteins specifically targeting mitochondrial inner membranes. Mitochondria share asexual budding with many bacterial endospores and membrane‐enveloped viruses. These megavirus−mitochondrion similarities are not coincidental: systematic alignment analyses have detected candidate megaviral homologs of each amoeban mitogene (including ribosomal RNAs) distributed across megaviral genomes. These candidate megaviral homologs overall follow mitogene order, and megaviral−mitogenome synteny increases with viral genome reduction. This analysis is repeated within Poxviridae , whose organellar‐like morphogenesis is reminiscent of mitochondria. More generally, the results confirm the patterns observed in Megavirales : synteny with amoeban mitogenomes increases with genome reduction. Parsimoniously interpreting this suggests Megavirales and mitochondria have a rickettsia‐like common ancestor. Megavirales could be the missing links between bacterial‐like cells and mitochondria, implying cellular‐to‐viral‐to‐subcellular macroevolution.