A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes

Abstract

While the circumstances surrounding the origin and spread of HIV are becoming clearer, the particulars of the origin of simian immunodeficiency virus (SIV) are still unknown. Specifically, the age of SIV, whether it is an ancient or recent infection, has not been resolved. Although many instances of cross-species transmission of SIV have been documented, the similarity between the African green monkey (AGM) and SIVagm phylogenies has long been held as suggestive of ancient codivergence between SIVs and their primate hosts. Here, we present well-resolved phylogenies based on full-length AGM mitochondrial genomes and seven previously published SIVagm genomes; these allowed us to perform the first rigorous phylogenetic test to our knowledge of the hypothesis that SIVagm codiverged with the AGMs. Using the Shimodaira-Hasegawa test, we show that the AGM mitochondrial genomes and SIVagm did not evolve along the same topology. Furthermore, we demonstrate that the SIVagm topology can be explained by a pattern of west-to-east transmission of the virus across existing AGM geographic ranges. Using a relaxed molecular clock, we also provide a date for the most recent common ancestor of the AGMs at approximately 3 million years ago. This study substantially weakens the theory of ancient SIV infection followed by codivergence with its primate hosts.

Figure 1. Phylogenetic Relationships among SIVagm Genomes

(A) SIVagm genomes and (B) SIVagm genomes plus two SIVver env genes from South Africa (SA). Both trees are shown with SIVsab as an outgroup, although midpoint rooting produces the same rooting pattern. ML nonparametric bootstrap support values (>50%) are shown on nodes.

Figure 2. Phylogenetic Relationships among AGM Nuclear Loci

(A) CD4 phylogeny and (B) CCR5 phylogeny. Both trees are midpoint rooted. ML nonparametric bootstrap support values (>50) are shown on nodes. “C. unknown” in (A) refers to a taxon with no published species-specific information.

Figure 3. Phylogenetic Relationships among AGM Mitochondrial Genomes

ML tree is shown with C. sabaeus taxa as an outgroup, although midpoint rooting produced the same rooting pattern. C. pygerythrus were isolated from Tanzania (TZ) and South Africa (SA). ML nonparametric bootstrap support values (>50%) are shown on nodes.

Figure 4. Relaxed Molecular Clock Analysis of Catarrhine Taxa with Estimated AGM Divergence Dates

ML tree is rooted using C. albifrons as an outgroup, with mean MRCA date for the AGM taxa and 95% confidence intervals estimated from 100 replicate trees from (a) ML bootstrap analysis and (b) Bayesian MCMC analysis. Asterisks designate nodes as being fossil-constrained as defined by Raaum et al. [42].

Figure 5. Hypothesized SIVagm Transmission Pattern across sub-Saharan Africa

AGM distributions across the African continent are depicted. According to SIVagm phylogenetic analysis, C. sabaeus was the first AGM to be infected with SIV, although the source of this infection is unknown. The arrows depict a possible route of transmission of the virus across already established AGM ranges. It should be noted that the inferred SIVagm phylogeny does not distinguish between the depicted route of transmission and a route in which C. tantalus first infected C. aethiops, which in turn infected C. pygerythrus. This figure is modified from Beer et al. [64], which utilized the range map from Lernould [12].