title: An evolutionary screen highlights canonical and noncanonical candidate antiviral genes within the primate TRIM gene family.
abstract: Recurrent viral pressure has acted on host-encoded antiviral genes during primate and mammalian evolution. This selective pressure has resulted in dramatic episodes of adaptation in host antiviral genes, often detected via positive selection. These evolutionary signatures of adaptation have the potential to highlight previously unrecognized antiviral genes (also called restriction factors). Although the TRIM multigene family is recognized for encoding several bona fide restriction factors (e.g., TRIM5alpha), most members of this expansive gene family remain uncharacterized. Here, we investigated the TRIM multigene family for signatures of positive selection to identify novel candidate antiviral genes. Our analysis reveals previously undocumented signatures of positive selection in 17 TRIM genes, 10 of which represent novel candidate restriction factors. These include the unusual TRIM52 gene, which has evolved under strong positive selection despite its encoded protein lacking a putative viral recognition (B30.2) domain. We show that TRIM52 arose via gene duplication from the TRIM41 gene. Both TRIM52 and TRIM41 have dramatically expanded RING domains compared with the rest of the TRIM multigene family, yet this domain has evolved under positive selection only in primate TRIM52, suggesting that it represents a novel host-virus interaction interface. Our evolutionary-based screen not only documents positive selection in known TRIM restriction factors but also highlights candidate novel restriction factors, providing insight into the interfaces of host-pathogen interactions mediated by the TRIM multigene family.
authors.affiliation: Department of Genome Sciences, University of Washington.
authors.forename: Ray
authors.initials: R
authors.lastname: Malfavon-Borja
authors.forename: Sara L
authors.initials: SL
authors.lastname: Sawyer
authors.forename: Lily I
authors.initials: LI
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
authors.forename: Harmit S
authors.initials: HS
authors.lastname: Malik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011323:Primates / Q000235:genetics* / Q000821:virology; D011485:Protein Binding; D054829:RING Finger Domains; D012641:Selection, Genetic; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C505879:TRIM41 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: TRIM5; TRIM52; dN/dS; positive selection; restriction factors