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Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae.

Västermark Å, Almén MS, Simmen MW, Fredriksson R, Schiöth HB - BMC Evol. Biol. (2011)

Bottom Line: We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains.We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought.The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. ake.vastermark@neuro.uu.se

ABSTRACT

Background: The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families.

Results: We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought.

Conclusions: The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA.

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Figure of edited EamA first domain maximum likelihood bootstrap forest. The red boxes indicate independent branches discovered in the edited dendrogram (AMAC, SLC35C/E, SLC35F). The oldest model organism sequence is indicated with an asterisk. Notable expansions, and the species involved, is shown with uppercase abbreviation followed by a plus (+) sign. The tree is rooted on the A. thaliana expansion. The yellow rings indicate bootstrap support in the 50-75% range and grey circles above 90%. AMAC stands for acyl-malonyl condensing enzyme, and PUP for purine permeases. The sequence RP11345P4.4 is annotated as SLC35E2B in GenBank. [additional file 9: supplementary table S6] lists which independent branches are present.
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Figure 2: Figure of edited EamA first domain maximum likelihood bootstrap forest. The red boxes indicate independent branches discovered in the edited dendrogram (AMAC, SLC35C/E, SLC35F). The oldest model organism sequence is indicated with an asterisk. Notable expansions, and the species involved, is shown with uppercase abbreviation followed by a plus (+) sign. The tree is rooted on the A. thaliana expansion. The yellow rings indicate bootstrap support in the 50-75% range and grey circles above 90%. AMAC stands for acyl-malonyl condensing enzyme, and PUP for purine permeases. The sequence RP11345P4.4 is annotated as SLC35E2B in GenBank. [additional file 9: supplementary table S6] lists which independent branches are present.

Mentions: Using the knowledge of the domain architecture, we then extracted just the first domain (here termed DMT-1) from the overall alignments obtained previously. We made 10 DMT dendrograms, such as the one shown in Figure 2, using the DMT-1 domains with RAxML [32]. We resolved the trees [additional file 6: supplementary figure S1; figure 2], i.e. ensured that they do not contain any nodes with bootstrap support <50%, using tools to edit the bootstrap forests (Methods; additional file 7: human_dmt-1.dendr.tgz). The number of sequences in the resolved tree is smaller than the original number of sequences because of the editing process [additional file 8: supplementary table S5].


Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae.

Västermark Å, Almén MS, Simmen MW, Fredriksson R, Schiöth HB - BMC Evol. Biol. (2011)

Figure of edited EamA first domain maximum likelihood bootstrap forest. The red boxes indicate independent branches discovered in the edited dendrogram (AMAC, SLC35C/E, SLC35F). The oldest model organism sequence is indicated with an asterisk. Notable expansions, and the species involved, is shown with uppercase abbreviation followed by a plus (+) sign. The tree is rooted on the A. thaliana expansion. The yellow rings indicate bootstrap support in the 50-75% range and grey circles above 90%. AMAC stands for acyl-malonyl condensing enzyme, and PUP for purine permeases. The sequence RP11345P4.4 is annotated as SLC35E2B in GenBank. [additional file 9: supplementary table S6] lists which independent branches are present.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111387&req=5

Figure 2: Figure of edited EamA first domain maximum likelihood bootstrap forest. The red boxes indicate independent branches discovered in the edited dendrogram (AMAC, SLC35C/E, SLC35F). The oldest model organism sequence is indicated with an asterisk. Notable expansions, and the species involved, is shown with uppercase abbreviation followed by a plus (+) sign. The tree is rooted on the A. thaliana expansion. The yellow rings indicate bootstrap support in the 50-75% range and grey circles above 90%. AMAC stands for acyl-malonyl condensing enzyme, and PUP for purine permeases. The sequence RP11345P4.4 is annotated as SLC35E2B in GenBank. [additional file 9: supplementary table S6] lists which independent branches are present.
Mentions: Using the knowledge of the domain architecture, we then extracted just the first domain (here termed DMT-1) from the overall alignments obtained previously. We made 10 DMT dendrograms, such as the one shown in Figure 2, using the DMT-1 domains with RAxML [32]. We resolved the trees [additional file 6: supplementary figure S1; figure 2], i.e. ensured that they do not contain any nodes with bootstrap support <50%, using tools to edit the bootstrap forests (Methods; additional file 7: human_dmt-1.dendr.tgz). The number of sequences in the resolved tree is smaller than the original number of sequences because of the editing process [additional file 8: supplementary table S5].

Bottom Line: We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains.We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought.The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. ake.vastermark@neuro.uu.se

ABSTRACT

Background: The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families.

Results: We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought.

Conclusions: The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA.

Show MeSH