Broad-scale phylogenomics provides insights into retrovirus-host evolution

Abstract

Genomic data provide an excellent resource to improve understanding of retrovirus evolution and the complex relationships among viruses and their hosts. In conjunction with broad-scale in silico screening of vertebrate genomes, this resource offers an opportunity to complement data on the evolution and frequency of past retroviral spread and so evaluate future risks and limitations for horizontal transmission between different host species. Here, we develop a methodology for extracting phylogenetic signal from large endogenous retrovirus (ERV) datasets by collapsing information to facilitate broad-scale phylogenomics across a wide sample of hosts. Starting with nearly 90,000 ERVs from 60 vertebrate host genomes, we construct phylogenetic hypotheses and draw inferences regarding the designation, host distribution, origin, and transmission of the Gammaretrovirus genus and associated class I ERVs. Our results uncover remarkable depths in retroviral sequence diversity, supported within a phylogenetic context. This finding suggests that current infectious exogenous retrovirus diversity may be underestimated, adding credence to the possibility that many additional exogenous retroviruses may remain to be discovered in vertebrate taxa. We demonstrate a history of frequent horizontal interorder transmissions from a rodent reservoir and suggest that rats may have acted as important overlooked facilitators of gammaretrovirus spread across diverse mammalian hosts. Together, these results demonstrate the promise of the methodology used here to analyze large ERV datasets and improve understanding of retroviral evolution and diversity for utilization in wider applications.

Fig. 1.

Retrovirus genera and ERV classes. Schematic illustrates the relationship among retroviral sequences, as recovered in Fig. S1. ERV classes associated with retroviral genera are indicated on branches.

Fig. 2.

ERV distribution among vertebrate host taxa. Vertebrate host phylogeny with corresponding pie charts illustrate the proportion of analyzed ERVs (outer circle), class I ERVs (inner circle), and the fraction of gamma-ERVs (red sector) for each genome. Circle size correlates with ERV counts according to the scale.

Fig. 3.

Gammaretrovirus phylogeny apex. Sequences from color-coded host genomes follow the short nomenclature outlined in Table S1. Hash marks in nomenclature precede the number of ERV sequences represented by each taxon. The expanded clades 1–3 are illustrated in Fig. S2, with loci details in Table S2. Colored circles indicate node support. Rat ERVs indicated by filled black circles frequently lie basally compared with the more numerous mouse sequences which are indicated by open circles.

Fig. 4.

Host–gammaretrovirus relationships. Tanglegram of host species and retroviruses illustrating host-switching events. ERVs present in rodent genomes suggest a pattern of extensive host switching. Rat ERVs are highlighted in boxes. Loci details for rat and mouse ERVs are presented in Table S2.