Limits...
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.

Show MeSH

Related in: MedlinePlus

Most parsimonious hypothesis to explain the diversification of the ubiquilin genes in animals. Arrow: origin of a new gene. Rectangle: gene loss. A single gene, which would be orthologous to vertebrate UBQLN4 was present when animals emerged.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Most parsimonious hypothesis to explain the diversification of the ubiquilin genes in animals. Arrow: origin of a new gene. Rectangle: gene loss. A single gene, which would be orthologous to vertebrate UBQLN4 was present when animals emerged.

Mentions: Taken all these results together, it is possible to formulate the most parsimonious hypothesis that explains the whole pattern of diversification observed in vertebrates, which is detailed in Figure 4. It is important that this hypothesis agrees perfectly with all the available information (phylogenetic reconstructions, genomic evidence and protein structure results). According to those data, from a single ancient vertebrate ubiquilin gene, UBQLN4, which would be orthologous to the only one present in non-vertebrate animals, we deduce the early generation of a first duplicate, UBQLN1, followed by the origination after the mammalia/sauropsida split of four additional mammalian-specific ubiquilin genes (first UBQLNL and later UBQLN2 as a UBQLN1 duplicate, and UBQLN3 and UBQLN5, which both derive from UBQLNL) and of the birth of a seventh gene, UBQLN6 in sauropsids. The evidence for an exceptional mammalian-specific increase in the number of ubiquilin genes is very robust, given the already extensive data for these species groups currently present in our databases. It is interesting to point out here the fact that the three genes for which there is evidence for an involvement in human neurodegenerative diseases, either potential or direct (UBQLN1, UBQLN2 and UBQLN4, see Introduction) have very similar UBA and UBL domains (see the small distances among them in Figure 3), encode structurally identical proteins and are related by successive duplications (UBQLN4 ➔ UBQLN1 ➔ UBQLN2). Their close relationships make advisable to call these three genes as “UBQLN4 group”. The genes of the UBQLNL group (UBQLNL, UBQLN3 and UBQLN5) have not so far been functionally linked to any human disease.


The ubiquilin gene family: evolutionary patterns and functional insights.

Marín I - BMC Evol. Biol. (2014)

Most parsimonious hypothesis to explain the diversification of the ubiquilin genes in animals. Arrow: origin of a new gene. Rectangle: gene loss. A single gene, which would be orthologous to vertebrate UBQLN4 was present when animals emerged.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Most parsimonious hypothesis to explain the diversification of the ubiquilin genes in animals. Arrow: origin of a new gene. Rectangle: gene loss. A single gene, which would be orthologous to vertebrate UBQLN4 was present when animals emerged.
Mentions: Taken all these results together, it is possible to formulate the most parsimonious hypothesis that explains the whole pattern of diversification observed in vertebrates, which is detailed in Figure 4. It is important that this hypothesis agrees perfectly with all the available information (phylogenetic reconstructions, genomic evidence and protein structure results). According to those data, from a single ancient vertebrate ubiquilin gene, UBQLN4, which would be orthologous to the only one present in non-vertebrate animals, we deduce the early generation of a first duplicate, UBQLN1, followed by the origination after the mammalia/sauropsida split of four additional mammalian-specific ubiquilin genes (first UBQLNL and later UBQLN2 as a UBQLN1 duplicate, and UBQLN3 and UBQLN5, which both derive from UBQLNL) and of the birth of a seventh gene, UBQLN6 in sauropsids. The evidence for an exceptional mammalian-specific increase in the number of ubiquilin genes is very robust, given the already extensive data for these species groups currently present in our databases. It is interesting to point out here the fact that the three genes for which there is evidence for an involvement in human neurodegenerative diseases, either potential or direct (UBQLN1, UBQLN2 and UBQLN4, see Introduction) have very similar UBA and UBL domains (see the small distances among them in Figure 3), encode structurally identical proteins and are related by successive duplications (UBQLN4 ➔ UBQLN1 ➔ UBQLN2). Their close relationships make advisable to call these three genes as “UBQLN4 group”. The genes of the UBQLNL group (UBQLNL, UBQLN3 and UBQLN5) have not so far been functionally linked to any human disease.

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