TRIM5 encodes proteins which exert antiviral activity against various retroviruses.TRIM5-Cyclophilin A(TRIMCyp)is a chimeric gene that arose independently in two primate lineages through a LINE-1-mediated retrotransposition of a cyclophilin A(CypA)processed pseudogene into TRIM5 locus,resulting in exon shuffling and protein fusion.The generation of TRIMCyp gene fusion is occurred independently in primate lineage,and certain TRIMCyp haplotypes encode fusion proteins with antiretroviral capabilities,with CypA acting as a capsid-binding domain,contributing to host intrinsic immunity.However,whether any TRIMCyp gene fusions existing outside primates remains unknown.By exploring 36 available mammalian genomes,we found a novel pattern of chimeric TRIMCyp that arose in non-primate tree shrews(Scandentia: Tupaiidae: Tupaia belangeri)by retrotransposing CypA into exon 8 of a TRIM5 duplicate gene.This event occurred after Scandentias divergence from Primates/Dermoptera,and this gene fusion is probably fixed in tree shrew population.Inserting CypA led to fusion transcripts,in this case,exons 2 to 7 of TRIM5 are fused with CypA cDNA,but missense mutations and nonsense mutations in CypA domain leads to truncation of tree shrew TRIMCyp.Moreover,we found that tree shrew TRIMCyp is expressed significantly higher in immune-related tissues and strong positive selection has been acting on the RBCC domains,which suggest that tree shrew TRIMCyp might had contributed to host immune defense.By contrast to the antiretroviral capacity of certain primate TRIMCyp haplotypes,over-expression of tree shrew TRIMCyp in permissive cells(CRFK)does not restrict HIV-1,SIVmac or N-MLV,likely due to the defective capsid-binding CypA domain.However,the reconstructed originally TRIMCyp was active against HIV-1.With gene duplication,retrotransposition and exon shuffling processes acting in combination,tree shrew TRIMCyp gene fusion was generated.Due to frameshifts and nonsense mutations,tree shrew TRIMCyp is truncated and lost the ability to restrict retroviruses.However,at the time of its birth,tree shrew TRIMCyp was active against certain viruses,which is consistent with its high distribution in immune-related tissues and may also explains why it underwent strong positive selection.More importantly,the origin of tree shrew TRIMCyp shed new light on how similar chimeric genes would be generated independently multiple times in different species in the long period of pathogen-host arms race.