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The ubiquilin gene family: evolutionary patterns and functional insights.

Marín I - BMC Evol. Biol. (2014)

Bottom Line: This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis.The ubiquilin gene family is highly conserved in eukaryotes.The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Valencia, Spain. imarin@ibv.csic.es.

ABSTRACT

Background: Ubiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood.

Results: In this study, evolutionary and functional data are combined to determine the origin and diversification of the ubiquilin gene family and to characterize novel potential roles of ubiquilins in mammalian species, including humans. The analysis of more than six hundred sequences allowed characterizing ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. fungi, many animals) have single ubiquilin genes, but duplications in animal, plant, alveolate and excavate species are described. Seven different ubiquilins have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, had not been hitherto described. Significantly, marsupial and eutherian mammals have the most complex ubiquilin gene families, composed of up to 6 genes. This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis. A gene with related features has independently arisen in species of the Drosophila genus. Positive selection acting on some mammalian ubiquilins has been detected.

Conclusions: The ubiquilin gene family is highly conserved in eukaryotes. The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues.

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Related in: MedlinePlus

Summary tree indicating the distribution of ubiquilins in eukaryotes. This is the neighbor-joining (NJ) tree, but the maximum-parsimony (MP) and maximum-likelihood (ML) dendrograms were similar enough as to allow all the results to be drawn together. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. A scale bar is shown below the tree. The numbers in the branches indicate bootstrap supports (in percentages) for the three methods of phylogenetic reconstruction (as follows: NJ/MP/ML). For simplicity, only the most relevant boostrap values are indicated. In brackets, the number of sequences within each group. These groups were made by putting together all the sequences that belonged to related species, in order to deduce the minimum number of groups for each eukaryotic class. Thus, all plant can be put in a single group, animal sequences can be classified into two groups, etc. For alveolates, stramenopiles and excavates, the main phyla that can be found within each group are indicated (in parentheses). A more detailed view of this tree can be found in Additional file 2.
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Figure 1: Summary tree indicating the distribution of ubiquilins in eukaryotes. This is the neighbor-joining (NJ) tree, but the maximum-parsimony (MP) and maximum-likelihood (ML) dendrograms were similar enough as to allow all the results to be drawn together. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. A scale bar is shown below the tree. The numbers in the branches indicate bootstrap supports (in percentages) for the three methods of phylogenetic reconstruction (as follows: NJ/MP/ML). For simplicity, only the most relevant boostrap values are indicated. In brackets, the number of sequences within each group. These groups were made by putting together all the sequences that belonged to related species, in order to deduce the minimum number of groups for each eukaryotic class. Thus, all plant can be put in a single group, animal sequences can be classified into two groups, etc. For alveolates, stramenopiles and excavates, the main phyla that can be found within each group are indicated (in parentheses). A more detailed view of this tree can be found in Additional file 2.

Mentions: In Figure 1, a compact view of the trees based on the UBL and UBA domains is shown (the whole, expanded view, including species names and accession numbers can be found as Additional file 2). The results suggested that the sequences present in animals, higher plants and fungi have a monophyletic origin, given that they appear together, as three independent groups, in those trees. The only apparent exceptions are a few Drosophila-specific duplicates that will be discussed below and the already mentioned Batrachochytrium sequence. It is true that these monophyletic origins are not fully demonstrated by the analyses, given that bootstrap support for the corresponding branches is low (Figure 1, Additional file 2). However, this was not unexpected, given the limited phylogenetic signal provided by the sequences of the UBL and UBA domains, which, together, have just around 120 amino acids. In any case, alternative hypotheses, based on multiple origins, are technically possible but clearly implausible given the available data. Along the next sections, all new evidence presented is, as will become apparent, fully coherent with these hypothesized monophyletic origins.


The ubiquilin gene family: evolutionary patterns and functional insights.

Marín I - BMC Evol. Biol. (2014)

Summary tree indicating the distribution of ubiquilins in eukaryotes. This is the neighbor-joining (NJ) tree, but the maximum-parsimony (MP) and maximum-likelihood (ML) dendrograms were similar enough as to allow all the results to be drawn together. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. A scale bar is shown below the tree. The numbers in the branches indicate bootstrap supports (in percentages) for the three methods of phylogenetic reconstruction (as follows: NJ/MP/ML). For simplicity, only the most relevant boostrap values are indicated. In brackets, the number of sequences within each group. These groups were made by putting together all the sequences that belonged to related species, in order to deduce the minimum number of groups for each eukaryotic class. Thus, all plant can be put in a single group, animal sequences can be classified into two groups, etc. For alveolates, stramenopiles and excavates, the main phyla that can be found within each group are indicated (in parentheses). A more detailed view of this tree can be found in Additional file 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230246&req=5

Figure 1: Summary tree indicating the distribution of ubiquilins in eukaryotes. This is the neighbor-joining (NJ) tree, but the maximum-parsimony (MP) and maximum-likelihood (ML) dendrograms were similar enough as to allow all the results to be drawn together. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. A scale bar is shown below the tree. The numbers in the branches indicate bootstrap supports (in percentages) for the three methods of phylogenetic reconstruction (as follows: NJ/MP/ML). For simplicity, only the most relevant boostrap values are indicated. In brackets, the number of sequences within each group. These groups were made by putting together all the sequences that belonged to related species, in order to deduce the minimum number of groups for each eukaryotic class. Thus, all plant can be put in a single group, animal sequences can be classified into two groups, etc. For alveolates, stramenopiles and excavates, the main phyla that can be found within each group are indicated (in parentheses). A more detailed view of this tree can be found in Additional file 2.
Mentions: In Figure 1, a compact view of the trees based on the UBL and UBA domains is shown (the whole, expanded view, including species names and accession numbers can be found as Additional file 2). The results suggested that the sequences present in animals, higher plants and fungi have a monophyletic origin, given that they appear together, as three independent groups, in those trees. The only apparent exceptions are a few Drosophila-specific duplicates that will be discussed below and the already mentioned Batrachochytrium sequence. It is true that these monophyletic origins are not fully demonstrated by the analyses, given that bootstrap support for the corresponding branches is low (Figure 1, Additional file 2). However, this was not unexpected, given the limited phylogenetic signal provided by the sequences of the UBL and UBA domains, which, together, have just around 120 amino acids. In any case, alternative hypotheses, based on multiple origins, are technically possible but clearly implausible given the available data. Along the next sections, all new evidence presented is, as will become apparent, fully coherent with these hypothesized monophyletic origins.

Bottom Line: This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis.The ubiquilin gene family is highly conserved in eukaryotes.The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Valencia, Spain. imarin@ibv.csic.es.

ABSTRACT

Background: Ubiquilins are proteins that function as ubiquitin receptors in eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the genesis of neurodegenerative diseases. However, ubiquilin functions are still poorly understood.

Results: In this study, evolutionary and functional data are combined to determine the origin and diversification of the ubiquilin gene family and to characterize novel potential roles of ubiquilins in mammalian species, including humans. The analysis of more than six hundred sequences allowed characterizing ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. fungi, many animals) have single ubiquilin genes, but duplications in animal, plant, alveolate and excavate species are described. Seven different ubiquilins have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, had not been hitherto described. Significantly, marsupial and eutherian mammals have the most complex ubiquilin gene families, composed of up to 6 genes. This exceptional mammalian-specific expansion is the result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise testis-specific expression patterns that indicate roles in the postmeiotic stages of spermatogenesis. A gene with related features has independently arisen in species of the Drosophila genus. Positive selection acting on some mammalian ubiquilins has been detected.

Conclusions: The ubiquilin gene family is highly conserved in eukaryotes. The infrequent lineage-specific amplifications observed may be linked to the emergence of novel functions in particular tissues.

Show MeSH
Related in: MedlinePlus