Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties

Abstract

BackgroundThe TRIM family is composed of multi-domain proteins that display the Tripartite Motif (RING, B-box and Coiled-coil) that can be associated with a C-terminal domain. TRIM genes are involved in ubiquitylation and are implicated in a variety of human pathologies, from Mendelian inherited disorders to cancer, and are also involved in cellular response to viral infection.ResultsHere we defined the entire human TRIM family and also identified the TRIM sets of other vertebrate (mouse, rat, dog, cow, chicken, tetraodon, and zebrafish) and invertebrate species (fruitfly, worm, and ciona). By means of comparative analyses we found that, after assembly of the tripartite motif in an early metazoan ancestor, few types of C-terminal domains have been associated with this module during evolution and that an important increase in TRIM number occurred in vertebrate species concomitantly with the addition of the SPRY domain. We showed that the human TRIM family is split into two groups that differ in domain structure, genomic organization and evolutionary properties. Group 1 members present a variety of C-terminal domains, are highly conserved among vertebrate species, and are represented in invertebrates. Conversely, group 2 is absent in invertebrates, is characterized by the presence of a C-terminal SPRY domain and presents unique sets of genes in each mammal examined. The generation of independent sets of group 2 genes is also evident in the other vertebrate species. Comparing the murine and human TRIM sets, we found that group 1 and 2 genes evolve at different speeds and are subject to different selective pressures.ConclusionWe found that the TRIM family is composed of two groups of genes with distinct evolutionary properties. Group 2 is younger, highly dynamic, and might act as a reservoir to develop novel TRIM functions. Since some group 2 genes are implicated in innate immune response, their evolutionary features may account for species-specific battles against viral infection.

The tripartite motif coiled-coil is an elongated antiparallel hairpin dimer

“…Thus, the TRIM domains are organized spatially, consistent with the idea that they have coevolved and behave as an integrated module, rather than as a collection of independent functional elements (14,20,48).…”

“…Sixty-seven members of the human TRIM family (table 1 in ref. 20), excluding TRIM25, were initially used to generate a multiple sequence alignment with the ClustalW2 program. (18).…”

“…TRIM proteins have been predicted to contain two distinct coiled-coil segments separated by a helical, but noncoil, segment (19,20). The TRIM25 structure reveals that these segments actually make up a single contiguous coil, helix H1, which forms the long arm of each subunit.…”

Molecular evolution of the antiretroviral TRIM5 gene

“…At least twice in the course of primate evolution TRIM5-cyclophilin A chimeric proteins arose via the capture of new exons (Brennan et al 2008;Liao et al 2007;Newman et al 2008;Nisole et al 2004;Sayah et al 2004;Virgen et al 2008;Wilson et al 2008b). The TRIM family is vigorously engaged in gene duplication Reymond et al 2001;Sardiello et al 2008), and in some mammalian genomes, expansions, inversions, and deletions of the TRIM5 locus itself are evident (Sawyer et al 2007;Tareen et al 2009). Given abundant evidence that retroviral pathogens have been ubiquitously present throughout primate evolution (Gifford and Tristem 2003;Johnson 2008;Lower et al 1996;Mager and Freeman 1995;Sverdlov 2000;Weiss 2006;Blikstad et al 2008), and the variety of retroviruses that are known to colonize extant primates (Vogt 1997), it is reasonable to hypothesize that primate TRIM5α has long played, and continues to play, a role in governing patterns of susceptibility to cross-species transmission and spread (within species) of retroviral pathogens (Song et al 2005a).…”

“…1), including (a) an amino-terminal RING domain, (b) one or two B-box domains, and (c) a long coiled-coil, which together constitute the canonical TRIM (tripartite) motif (Reymond et al 2001;Sardiello et al 2008). Most TRIM genes encode an additional C-terminal domain, which in many cases is a B30.2 domain Reymond et al 2001;Rhodes et al 2005;Sardiello et al 2008). The TRIM5 gene encodes multiple protein isoforms.…”