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

Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G - BMC Evol. Biol. (2008)

Bottom Line: 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.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.We found that the TRIM family is composed of two groups of genes with distinct evolutionary properties.

View Article: PubMed Central - HTML - PubMed

Affiliation: Telethon Institute of Genetics and Medicine, Via P, Castellino 111, 80131 Naples, Italy. sardiello@tigem.it

ABSTRACT

Background: The 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.

Results: Here 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.

Conclusion: We 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.

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Phylogenetic analysis of human (h, blue), mouse (m, blue), fruitfly (CGs, red), and worm (green) group 1 TRIM and TRIM-like proteins. Human and mouse TRIM proteins are indicated with their TRIM numbers; 'incomplete' TRIM proteins are indicated with their alternative TRIM number with an asterisk (see Table 1); fruitfly and worm sequences are indicated with GenBank accession numbers. Bootstrap support values above 50% based on 1000 replicates are shown. The main domain distal to the tripartite motif is indicated on the right; ND indicates no known domain detected. Panels A-E show the evolutionary relationships among the members of TRIM subgroups that belong to group 1; the worm TRIM genes composed of the R-B2-CC motif only (Figure 2B) represent a separate group related to group 1 and are not shown in the figure. TRIM37 (C-terminal domain: MATH) did not segregated within any subgroups in preliminary analyses and was therefore used as an outgroup in all phylogenetic analyses. The trees were drawn to the scale of amino acid sequence divergence indicated at the bottom right corner. A) Subgroup A includes FN3 and FN3-related TRIM sequences. Fruitfly CG31721 and its worm ortholog C39F7 are the only invertebrate proteins present in the FN3 subgroup and segregate with mammalian TRIM9 and 67. B) Subgroup B includes ARF-related TRIM sequences. Genes encoding a protein homologous to TRIM23 are found in worm and in the honeybee Apis mellifera (ENS10667 = ENSAPMT00000010667) but not in D. melanogaster, suggesting that the ARF domain has been acquired by a tripartite-gene precursor before vertebrate-invertebrate lineage separation, and has occasionally been lost in some species. C) Subgroup C includes PHD-BROMO and PHD-BROMO-related TRIM sequences. Fruitfly CG5206 behaves as an outgroup for all human and mouse PHD-BROMO proteins, suggesting that it may be regarded as an ortholog of their protein ancestor. D) Subgroup D includes IGFLMN-related TRIM sequences. This subgroup is the only example of TRIM expansion in invertebrates, because it includes worm and fly genes that do not have any direct correspondent in mammals. E) Subgroup E includes TRIM proteins with B1, B2, and SPRY in various combinations (see Table 1). No invertebrate sequences are found within this subgroup.
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Figure 4: Phylogenetic analysis of human (h, blue), mouse (m, blue), fruitfly (CGs, red), and worm (green) group 1 TRIM and TRIM-like proteins. Human and mouse TRIM proteins are indicated with their TRIM numbers; 'incomplete' TRIM proteins are indicated with their alternative TRIM number with an asterisk (see Table 1); fruitfly and worm sequences are indicated with GenBank accession numbers. Bootstrap support values above 50% based on 1000 replicates are shown. The main domain distal to the tripartite motif is indicated on the right; ND indicates no known domain detected. Panels A-E show the evolutionary relationships among the members of TRIM subgroups that belong to group 1; the worm TRIM genes composed of the R-B2-CC motif only (Figure 2B) represent a separate group related to group 1 and are not shown in the figure. TRIM37 (C-terminal domain: MATH) did not segregated within any subgroups in preliminary analyses and was therefore used as an outgroup in all phylogenetic analyses. The trees were drawn to the scale of amino acid sequence divergence indicated at the bottom right corner. A) Subgroup A includes FN3 and FN3-related TRIM sequences. Fruitfly CG31721 and its worm ortholog C39F7 are the only invertebrate proteins present in the FN3 subgroup and segregate with mammalian TRIM9 and 67. B) Subgroup B includes ARF-related TRIM sequences. Genes encoding a protein homologous to TRIM23 are found in worm and in the honeybee Apis mellifera (ENS10667 = ENSAPMT00000010667) but not in D. melanogaster, suggesting that the ARF domain has been acquired by a tripartite-gene precursor before vertebrate-invertebrate lineage separation, and has occasionally been lost in some species. C) Subgroup C includes PHD-BROMO and PHD-BROMO-related TRIM sequences. Fruitfly CG5206 behaves as an outgroup for all human and mouse PHD-BROMO proteins, suggesting that it may be regarded as an ortholog of their protein ancestor. D) Subgroup D includes IGFLMN-related TRIM sequences. This subgroup is the only example of TRIM expansion in invertebrates, because it includes worm and fly genes that do not have any direct correspondent in mammals. E) Subgroup E includes TRIM proteins with B1, B2, and SPRY in various combinations (see Table 1). No invertebrate sequences are found within this subgroup.

Mentions: Preliminary rounds of sequence alignment and evolutionary analyses allowed us to divide the TRIM and TRIM-like family members into major classes and subsequently generate their phylogenetic trees separately using the full-length protein sequences from man, mouse, fruitfly and worm (see Methods for details). The results show that these proteins are evolutionarily organized in two groups that coincide with group 1 and group 2 (Fig. 4 and 5). The only discrepancy with the previous subdivision is TRIM62, which segregates with group 2 proteins in the evolutionary analysis. Within group 1, TRIM37 did not segregate with any subgroups in preliminary studies and therefore it was used as an outgroup in all phylogenetic analyses.


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

Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G - BMC Evol. Biol. (2008)

Phylogenetic analysis of human (h, blue), mouse (m, blue), fruitfly (CGs, red), and worm (green) group 1 TRIM and TRIM-like proteins. Human and mouse TRIM proteins are indicated with their TRIM numbers; 'incomplete' TRIM proteins are indicated with their alternative TRIM number with an asterisk (see Table 1); fruitfly and worm sequences are indicated with GenBank accession numbers. Bootstrap support values above 50% based on 1000 replicates are shown. The main domain distal to the tripartite motif is indicated on the right; ND indicates no known domain detected. Panels A-E show the evolutionary relationships among the members of TRIM subgroups that belong to group 1; the worm TRIM genes composed of the R-B2-CC motif only (Figure 2B) represent a separate group related to group 1 and are not shown in the figure. TRIM37 (C-terminal domain: MATH) did not segregated within any subgroups in preliminary analyses and was therefore used as an outgroup in all phylogenetic analyses. The trees were drawn to the scale of amino acid sequence divergence indicated at the bottom right corner. A) Subgroup A includes FN3 and FN3-related TRIM sequences. Fruitfly CG31721 and its worm ortholog C39F7 are the only invertebrate proteins present in the FN3 subgroup and segregate with mammalian TRIM9 and 67. B) Subgroup B includes ARF-related TRIM sequences. Genes encoding a protein homologous to TRIM23 are found in worm and in the honeybee Apis mellifera (ENS10667 = ENSAPMT00000010667) but not in D. melanogaster, suggesting that the ARF domain has been acquired by a tripartite-gene precursor before vertebrate-invertebrate lineage separation, and has occasionally been lost in some species. C) Subgroup C includes PHD-BROMO and PHD-BROMO-related TRIM sequences. Fruitfly CG5206 behaves as an outgroup for all human and mouse PHD-BROMO proteins, suggesting that it may be regarded as an ortholog of their protein ancestor. D) Subgroup D includes IGFLMN-related TRIM sequences. This subgroup is the only example of TRIM expansion in invertebrates, because it includes worm and fly genes that do not have any direct correspondent in mammals. E) Subgroup E includes TRIM proteins with B1, B2, and SPRY in various combinations (see Table 1). No invertebrate sequences are found within this subgroup.
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Figure 4: Phylogenetic analysis of human (h, blue), mouse (m, blue), fruitfly (CGs, red), and worm (green) group 1 TRIM and TRIM-like proteins. Human and mouse TRIM proteins are indicated with their TRIM numbers; 'incomplete' TRIM proteins are indicated with their alternative TRIM number with an asterisk (see Table 1); fruitfly and worm sequences are indicated with GenBank accession numbers. Bootstrap support values above 50% based on 1000 replicates are shown. The main domain distal to the tripartite motif is indicated on the right; ND indicates no known domain detected. Panels A-E show the evolutionary relationships among the members of TRIM subgroups that belong to group 1; the worm TRIM genes composed of the R-B2-CC motif only (Figure 2B) represent a separate group related to group 1 and are not shown in the figure. TRIM37 (C-terminal domain: MATH) did not segregated within any subgroups in preliminary analyses and was therefore used as an outgroup in all phylogenetic analyses. The trees were drawn to the scale of amino acid sequence divergence indicated at the bottom right corner. A) Subgroup A includes FN3 and FN3-related TRIM sequences. Fruitfly CG31721 and its worm ortholog C39F7 are the only invertebrate proteins present in the FN3 subgroup and segregate with mammalian TRIM9 and 67. B) Subgroup B includes ARF-related TRIM sequences. Genes encoding a protein homologous to TRIM23 are found in worm and in the honeybee Apis mellifera (ENS10667 = ENSAPMT00000010667) but not in D. melanogaster, suggesting that the ARF domain has been acquired by a tripartite-gene precursor before vertebrate-invertebrate lineage separation, and has occasionally been lost in some species. C) Subgroup C includes PHD-BROMO and PHD-BROMO-related TRIM sequences. Fruitfly CG5206 behaves as an outgroup for all human and mouse PHD-BROMO proteins, suggesting that it may be regarded as an ortholog of their protein ancestor. D) Subgroup D includes IGFLMN-related TRIM sequences. This subgroup is the only example of TRIM expansion in invertebrates, because it includes worm and fly genes that do not have any direct correspondent in mammals. E) Subgroup E includes TRIM proteins with B1, B2, and SPRY in various combinations (see Table 1). No invertebrate sequences are found within this subgroup.
Mentions: Preliminary rounds of sequence alignment and evolutionary analyses allowed us to divide the TRIM and TRIM-like family members into major classes and subsequently generate their phylogenetic trees separately using the full-length protein sequences from man, mouse, fruitfly and worm (see Methods for details). The results show that these proteins are evolutionarily organized in two groups that coincide with group 1 and group 2 (Fig. 4 and 5). The only discrepancy with the previous subdivision is TRIM62, which segregates with group 2 proteins in the evolutionary analysis. Within group 1, TRIM37 did not segregate with any subgroups in preliminary studies and therefore it was used as an outgroup in all phylogenetic analyses.

Bottom Line: 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.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.We found that the TRIM family is composed of two groups of genes with distinct evolutionary properties.

View Article: PubMed Central - HTML - PubMed

Affiliation: Telethon Institute of Genetics and Medicine, Via P, Castellino 111, 80131 Naples, Italy. sardiello@tigem.it

ABSTRACT

Background: The 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.

Results: Here 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.

Conclusion: We 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.

Show MeSH
Related in: MedlinePlus