Abstract
The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio) and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5–6 million years before present (ybp), likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species.
Highlights
Primates have been infected with retroviruses frequently throughout their evolution
We find that all samples lack the cyclophilin A (CypA) insertion in the TRIM5 39 untranslated region (UTR), the splice site single nucleotide polymorphism (SNP) associated with TRIMCyp, and TRIMCyp expression
Baboons lack TRIMCyp and the CypA insertion Old World primate TRIMCyp has so far been found in Asian macaques, and not in sooty mangabeys, which are African primates that belong to the papionin clade, a sister clade to the macaques
Summary
Retroviral infections are believed to have driven the evolution of host factors such as the restriction factors TRIM5a and TRIMCyp [1]. TRIM5a and TRIMCyp are two of several alternatively spliced isoforms of the TRIM5 gene [8]. TRIM5a has a Cterminal B30.2/SPRY domain, which recognizes and binds to the capsids of susceptible retroviruses, leading to post-entry restriction of infection [8,10,11]. This restriction occurs in a two-stage process, with stages both before and after reverse transcription [2,4,12]
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