title: Birth, decay, and reconstruction of an ancient TRIMCyp gene fusion in primate genomes.
abstract: TRIM5 is a host antiviral gene with an evolutionary history of genetic conflict with retroviruses. The TRIMCyp gene encodes a protein fusion of TRIM5 effector domains with the capsid-binding ability of a retrotransposed CyclophilinA (CypA), resulting in novel antiviral specificity against lentiviruses. Previous studies have identified two independent primate TRIMCyp fusions that evolved within the past 6 My. Here, we describe an ancient primate TRIMCyp gene (that we call TRIMCypA3), which evolved in the common ancestor of simian primates 43 Mya. Gene reconstruction shows that CypA3 encoded an intact, likely active, TRIMCyp antiviral gene, which was subject to selective constraints for at least 10 My, followed by pseudogenization or loss in all extant primates. Despite its decayed status, we found TRIMCypA3 gene fusion transcripts in several primates. We found that the reconstructed "newly born" TrimCypA3 encoded robust and broad retroviral restriction activity but that this broad activity was lost via eight amino acid changes over the course of the next 10 My. We propose that TRIMCypA3 arose in response to a viral pathogen encountered by ancestral primates but was subsequently pseudogenized or lost due to a lack of selective pressure. Much like imprints of ancient viruses, fossils of decayed genes, such as TRIMCypA3, provide unique and specific insight into paleoviral infections that plagued primates deep in their evolutionary history.
authors: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors: Ray
authors: R
authors: Malfavon-Borja
authors: Lily I
authors: LI
authors: Wu
authors: Michael
authors: M
authors: Emerman
authors: Harmit Singh
authors: HS
authors: Malik
mesh_terms: D000818:Animals; D001483:Base Sequence; D021984:Cyclophilin A / Q000235:genetics* / Q000276:immunology; D019143:Evolution, Molecular; D050939:Gene Fusion / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D011323:Primates / Q000235:genetics* / Q000821:virology; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D012190:Retroviridae / Q000276:immunology*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases
chemical_list: D011506:Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A