Comprehensive phylogenomic analysis reveals a novel cluster of simian endogenous retroviral sequences in Colobinae monkeys

Abstract

Simian retrovirus (SRV) is a type-D betaretrovirus infectious to the Old World monkeys causing a variety of symptoms. SRVs are also present in the Old World monkey genomes as endogenous forms, which are referred to as Simian endogenous retroviruses (SERVs). Although many SERV sequences have been identified in Cercopithecinae genomes, with potential of encoding all functional genes, the distribution of SERVs in genomes and evolutionary relationship between exogeneous SRVs and SERVs remains unclear. In this study, we comprehensively investigated seven draft genome sequences of the Old World monkeys, and identified a novel cluster of SERVs in the two Rhinopithecus (R. roxellana and R. bieti) genomes, which belong to the Colobinae subfamily. The Rhinopithecus genomes harbored higher copy numbers of SERVs than the Cercopithecinae genomes. A reconstructed phylogenetic tree showed that the Colobinae SERVs formed a distinct cluster from SRVs and Cercopithecinae SERVs, and more closely related to exogenous SRVs than Cercopithecinae SERVs. Three radical amino acid substitutions specific to Cercopithecinae SERVs, which potentially affect the infectious ability of SERVs, were also identified in the proviral envelope protein. In addition, we found many integration events of SERVs were genus- or species-specific, suggesting the recent activity of SERVs in the Old World monkey genomes. The results suggest that SERVs in Cercopithecinae and Colobinae monkeys were endogenized after the divergence of subfamilies and do not transmit across subfamilies. Our findings also support the hypothesis that Colobinae SERVs are direct ancestors of SRV-6, which has a different origin from the other exogenous SRVs. These findings shed novel insight into the evolutionary history of SERVs, and may help to understand the process of endogenization of SRVs.

Contemporary Distribution, Estimated Age, and Prehistoric Migrations of Old World Monkey Retroviruses

“…In contrast, in Theropithecus and Chlorocebus there are also a few proviruses with only 1-2 nt substitutions between the LTRs (unpublished observation), indeed pointing to a lengthy period of germ line activity. Rhinopithecus roxellana SERV integrations with open reading frames were found to be significantly younger than the ones with frame-shift mutations [132]. Furthermore, heterozygous SERV insertions are presumed to be more recent than integrations that have been fixed in a population.…”

“…Similar to PcEV, SERV, a full-length integrated type D betaretrovirus was first described from a baboon genomic library [38]. Subsequently, a widespread distribution in OWM with a relatively large nucleotide divergence between the viral sequences suggested a relative old age for the proviruses (Table 2) [38,132]. Heterozygous integrations abound, at least in Chlorocebus sabaeus, which suggests that many are so recent that they have not had sufficient time to become fixed in the population [128].…”

“…Full-length proviruses, intact reading frames, virus expression and heterozygous insertions do suggest a young age, but SERV has been calculated to have integrated on average 6.16 ± 3.41 (range 0-21.62) mya in Asian colobines, which, however, carry a distinct variant of SERV, and somewhat later, 3.42 ± 2.20 (range 0.27-14.09) mya, in cercopithecine species; that is, monkeys of the subfamily Cercopithecinae; thus, both Cercopithecini and Papionini [132]. It was therefore suggested that SERV originated within the last 8 million years and continued its exogenous activity until quite recently.…”

“…It was therefore suggested that SERV originated within the last 8 million years and continued its exogenous activity until quite recently. For instance, in Asian colobines, species specific, genus specific, but also shared integrations are seen [132]. Highly divergent SERV 5 and 3 LTRs can be found in cercopithecines.…”

Analysis of Simian Endogenous Retrovirus (SERV) proviruses in Old World Monkey Genomes: Evidence for a Transition to Replication during Embryogenesis

“…Full length or nearly full length SERV proviral genomes are found in many OWM species, with up to 80, mostly heterozygous, integrations detected in individual monkeys [6]. A variant SERV, col-SERV, with full length integrations and substantial homology to SRV-6 (simian type D retrovirus-6), was reported from the Asian Colobine species Rhinopithecus roxellana and R. bieti, with incomplete proviruses being present in Nasalis larvatus [7]. Phylogenetic analysis suggested that Col-SERV had spread between and integrated in the genome of Colobine ancestors after the separation of Cercopithecinae and Colobinae, which has been estimated to have occurred approximately 16 mya [7,8].…”