A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

The ABEV group was followed by the appearance of the ABE group. The first FSF in ABE was the "ACT-like" FSF (d.58.18), which includes regulatory protein domains mainly involved in amino acid metabolism and transport. We propose that d.58.18 was most likely "lost" (or never gained) in ancient viruses because simultaneous gain in three superkingdoms is less likely than loss in just one superkingdom. By extension, the appearance of the BEV group with the inception of the "Lysozyme-like" FSF (d.2.1) at nd = 0.15 signals the loss of the first FSF in a cellular superkingdom (Archaea). Simply, the absence of an ancient FSF in one group (out of three or four groups) is more likely a result of reductive evolution than separate gains [as previously described (18)]. The previously reconstructed proteome of the last common ancestor of Archaea, Bacteria, and Eukarya was reported to encode a minimum of 70 FSFs (57) . The most recent of those FSFs, "Terpenoid synthases" FSF (a.128.1), appeared at nd = 0.19 and was absent in all viruses, except one (African swine fever virus). These events demonstrate the early reductive In comparison, FSFs unique to superkingdoms and the viral supergroup appeared much later (see the A, B, E, and V groups in Fig. 5A ). These gains signaled the diversification of that superkingdom or supergroup. The late appearance of VSFs (V group in Fig. 5A ) is interesting because it includes FSFs involved in viral pathogenicity (Tables 1 and 2 ). The phylogenomic analysis shows that VSFs originated at the same time or after the diversification of modern cells. Thus, they represent the time point when proto-virocells, under prolonged genome reduction pressure, completely lost their cellular nature and became fully dependent on emerging archaeal, bacterial, and eukaryal cells for reproduction. This idea is strengthened by the evolutionary appearances of the AV, BV, and EV groups soon after the FSFs of the superkingdom-specific A, B, and E groups, respectively (see patterned regions in Fig. 5A ). We speculate that FSFs in the AV, BV, and EV groups either perform functions required by viruses to successfully infect their hosts (for example, BV FSFs that perform viral functions) or are simply HGT gains from their hosts. We have already discussed the composition of the BV group, which includes~60% FSFs of viral origin (Table 1) . Similarly, the AV and EV groups also include viral FSFs, albeit in lower numbers ( S7) . It is possible that this repertoire was provided to eukaryotes from viruses or was simply gained in eukaryoviruses from their eukaryotic hosts through HGT. In turn, no biological process was enriched in either AV or BV. Next, we divided viral FSFs into four subgroups: (i) those shared between prokaryotic viruses and eukaryoviruses (that is, the abe core of Fig. 3B; table S5 ); (ii) other viral FSFs shared with cells (cyan circles); (iii) VSFs (green circles); and (iv) FSFs not detected in viral proteomes (black circles) (Fig. 5B) . Generally, FSFs of the abe core were present in a greater number of viral proteomes (higher f values) and in more replicon types ( fig. S3) . Some of the most popular FSFs again included the P-loop containing NTP hydrolase (c.37.1), DNA/ RNA polymerases (e.8.1), and Ribonuclease H-like (c.55.3) FSFs. In turn, FSFs shared with cells were relatively less widespread. However, the Lysozyme-like FSF (d.2.1) was detected in a large number of viruses (18%), mostly bacterioviruses. Lysozymes can penetrate