A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

To infer the predominant direction of gene transfer (that is, virus to cell or cell to virus), we divided FSFs in each superkingdom into two sets: (i) those shared only with cells and (ii) those also shared with viruses. FSFs specific for each superkingdom (that is, A, B, and E Venn groups in Fig. 1A ) were excluded because they represent gains unique to each superkingdom and de facto could not be subject to horizontal transfers unless they were later completely lost from the donor superkingdom. A total of 1022 FSFs were encoded by archaeal proteomes. After the exclusion of 24 Archaea-specific FSFs, 533 (52%) were shared only with Bacteria and Eukarya and 465 (45%) were also shared with viruses. Similarly, of 1535 total bacterial FSFs, 154 were Bacteria-specific, 786 (51%) were shared only with Archaea and Eukarya, and 595 (39%) were also shared with viruses. Finally, eukaryal proteomes encoded a total of 1661 FSFs, including 283 that were Eukarya-specific, 774 (47%) that were shared only with the superkingdoms Archaea and Bacteria, and 604 (36%) that were also shared with viruses. Next, we calculated a fractional (f ) value to determine the spread of FSFs in the proteomes of each superkingdom (Fig. 2 ). The f value gives the spread of each FSF in modern proteomes and ranges from 0 (complete absence in sampled proteomes) to 1 (present in all proteomes). In all superkingdoms, FSFs shared with viruses were significantly more widespread in proteomes than those shared only with cells. The median f value in Archaea for FSFs shared only with cells was 0.45, in comparison to 0.59 for FSFs shared with viruses (that is, a 31% increase in spread). Similarly, medians increased from 0.30 to 0.62 (up by 106%) in Bacteria and increased most significantly from 0.39 to 0.93 (up by 138%) in Eukarya ( Fig. 2A) . Regardless of the numerical differences between superkingdoms, FSFs shared with viruses were significantly more widespread in individual members of each superkingdom. One explanation is that viruses mediated the spread of these FSFs by serving as vehicles of gene transfer. It also suggests that viruses are very ancient and most likely infected the last common ancestor of each superkingdom because viral FSFs were present in a diverse array of cellular organisms ranging from small microbes to large eukaryotes. A breakdown by viral replicon type provided additional insights (Fig. 2B ). In Archaea, nearly all of the viral FSFs were well represented in member species. Surprisingly, FSFs shared with RNA viruses were also enriched in archaeal proteomes. Because RNA viruses seemingly cannot carry out a productive infectious life cycle in Archaea (read below), it is unlikely that they picked these FSFs from archaeal hosts through HGT. In turn, it is more likely that RNA viruses infecting different superkingdoms share FSFs that were retained during their evolution from ancient cells. Similar patterns were also seen in bacterial proteomes (Fig. 2B ). Remarkably, FSFs shared with each viral replicon type were almost universal ( f approaching 1) among members of the Eukarya superkingdom. As we will now show, this is consistent with Eukarya hosting a large number of viruses from each replicon type.