Do Viruses Exchange Genes across Superkingdoms of Life?

Malik, Shahana S.; Azem-e-Zahra, Syeda; Kim, Kyung Mo; Caetano-Anollés, Gustavo; Nasir, Arshan

Finally, we only considered f -values of virus-encoded FSFs in cellular proteomes and not in viral proteomes. Viruses are notorious for encoding small-sized genomes that are likely a result of extreme genome reduction (Nasir et al., 2012a; Claverie and Abergel, 2013) . In a recent analysis, we showed that only three viral FSFs had an f -value of over 0.3 (Nasir and Caetano-Anollés, 2015) . This result is unsurprising considering that the 3,440 viruses of this study belong to seven different replication strategies, infect the many diverse groups of cellular organisms (see Nasir et al., 2014 for a mapping of virus replicons to their hosts), and in general harbor genomes and particle sizes that are minimalistic. The tendency of viruses to reduce genome size over long evolutionary timespans has effectively led to loss of information when extant virus genomes are comparatively analyzed with cellular genomes. Indeed, no single FSF could be detected in all seven viral replicon types (Nasir and Caetano-Anollés, 2015) . Therefore, we caution the readers that the strategy reported in this study takes a modern-day snapshot of the proteomes of both viruses and cellular organisms and does not benefit from phylogenomic reconstruction. It is also dependent on the size of available genomic databases that are severely underrepresented, especially, in archaeal and viral genome sequences. However, we do not expect that sequencing and discovery of novel viral and cellular lineages will drastically compromise our conclusions since we used a very strict threshold (e.g., f < 1%) in classifying an FSF to be acquired horizontally from viruses along with investigation of its biochemical function (e.g., virion synthesis). That is, future discovery of a virushallmark FSF in hundreds of newly sequenced genomes of a superkingdom that would significantly increase the f -values should be considered a highly unlikely event. However, discovery of novel viruses/cellular lineages can definitely add more virus-derived genes in cellular organisms thus adding to the lists of virus-acquired genes in cells or virus-specific genes ( Table 2) . Moreover, we restricted our analysis to the reference genomes of viruses and corresponding host organisms and to coding DNA. The next logical step is to perform a similar exercise on viruses recovered from metagenomic samples that are increasingly populating bioinformatics databases due to the continuous decline in sequencing cost and availability of fast and reliable high-throughput sequencing platforms. However, it can be sometimes challenging to establish host tropism in metagenome samples. Furthermore, there is no single universal gene (i.e., ribosomal RNA gene in cellular organisms) that can taxonomically classify short sequencing reads of viral metagenomes (Rohwer and Edwards, 2002) . That is why we restricted our analysis to only well-curated reference genomes with virus host information available from experimental studies. Similarly, many viral genetic elements are permanently integrated into cellular genomes (Katzourakis and Gifford, 2010) . This DNA also originated in viruses and thus should be considered the horizontal transfer of non-coding virus-to-cell transfer. While the virology community remains divided whether or not to include viruses in the realm of life (Claverie and Ogata, 2009; Moreira and Lopez-Garcia, 2009; Forterre, 2016) , there have been recent important phylogenomic data-driven breakthroughs unfolding viral or