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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

Dendrogram corresponding to the five human ubiquilin genes and their orthologs in rat. In parenthesis, accession numbers of the sequences. The tree shown here was obtained with the NJ method, but ML and MP analyses generated exactly the same topology. Branches 1–4 are those in which potential positive selection (ω > 1) was detected in PAML analyses. The observed ω values in the three different branch models [63] tested are also indicated. See text for details.
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Figure 10: Dendrogram corresponding to the five human ubiquilin genes and their orthologs in rat. In parenthesis, accession numbers of the sequences. The tree shown here was obtained with the NJ method, but ML and MP analyses generated exactly the same topology. Branches 1–4 are those in which potential positive selection (ω > 1) was detected in PAML analyses. The observed ω values in the three different branch models [63] tested are also indicated. See text for details.

Mentions: I checked whether positive selection was detectable on the sequences of human ubiquilin genes following standard procedures. First, the conserved UBL and UBA domains of the five human genes (UBQLN1, UBQLN2, UBQLN3, UBQLN4 and UBQLNL) and their rat orthologs were aligned. The phylogenetic trees that these sequences generated were of course congruent with the expectations derived from Figure 4: UBQLN4 may correspond to the oldest gene, while UBQLN1 and UBQLN2 is a relatively recent couple of paralogs and UBQLNL and UBQLN3, a second paralog duo (Figure 10). From the protein sequences of the UBL and UBA domains of those 10 genes, I obtained the corresponding nucleotide sequences and then performed codon-based analyses for positive selection using the CODEML program of the PAML package [63,64] and references therein]. Analyses were made using a recently generated graphical interface for PAML, called PAMLX [65].


The ubiquilin gene family: evolutionary patterns and functional insights.

Marín I - BMC Evol. Biol. (2014)

Dendrogram corresponding to the five human ubiquilin genes and their orthologs in rat. In parenthesis, accession numbers of the sequences. The tree shown here was obtained with the NJ method, but ML and MP analyses generated exactly the same topology. Branches 1–4 are those in which potential positive selection (ω > 1) was detected in PAML analyses. The observed ω values in the three different branch models [63] tested are also indicated. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Dendrogram corresponding to the five human ubiquilin genes and their orthologs in rat. In parenthesis, accession numbers of the sequences. The tree shown here was obtained with the NJ method, but ML and MP analyses generated exactly the same topology. Branches 1–4 are those in which potential positive selection (ω > 1) was detected in PAML analyses. The observed ω values in the three different branch models [63] tested are also indicated. See text for details.
Mentions: I checked whether positive selection was detectable on the sequences of human ubiquilin genes following standard procedures. First, the conserved UBL and UBA domains of the five human genes (UBQLN1, UBQLN2, UBQLN3, UBQLN4 and UBQLNL) and their rat orthologs were aligned. The phylogenetic trees that these sequences generated were of course congruent with the expectations derived from Figure 4: UBQLN4 may correspond to the oldest gene, while UBQLN1 and UBQLN2 is a relatively recent couple of paralogs and UBQLNL and UBQLN3, a second paralog duo (Figure 10). From the protein sequences of the UBL and UBA domains of those 10 genes, I obtained the corresponding nucleotide sequences and then performed codon-based analyses for positive selection using the CODEML program of the PAML package [63,64] and references therein]. Analyses were made using a recently generated graphical interface for PAML, called PAMLX [65].

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