Speaker
Description
Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across metagenomes. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 novel anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus clades: alpha, beta and gammatorquevirus, while we also present one new genome of the under-sampled hetorquevirus clade. The phylogeny reconstructed from the conserved ORF1 gene reveals three additional, previously undescribed human anellovirus clades with potential evidence of ancestral recombination. We performed detailed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same clade and only 15 inter-clade recombination events were confidently detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, with the ORF1 coding region being a recombination coldspot. Our analysis suggests that anellovirus evolution is governed by homologous recombination, however events between distant viruses or ones producing chimaeric ORF1s likely lead to non-viable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses' rolling-circle replication. A subset of the genomes assembled in both this and previous studies is completely lacking the replication loop, opening up the possibility that anellovirus intracellular populations contain non-replicating, defective virus genomes (DVGs). Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.
