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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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TBLASTN 2.2.24+ confirmatory search of oldest model organism sequence identified in subfamilies in edited EamA dendrogram. Using TBLASTN 2.2.24+, the human sequences of TMEM20 and SLC35E1, representing the "AMAC" and "SLC35C/E" subfamilies, are used as query against a set of 12 new model organisms (left column). Any shift in divergence time (from H. sapiens), compared to the corresponding organism in the (ordinal) set of model organisms (Methods), is indicated in the right hand column, with data from TimeTree [35].
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Figure 4: TBLASTN 2.2.24+ confirmatory search of oldest model organism sequence identified in subfamilies in edited EamA dendrogram. Using TBLASTN 2.2.24+, the human sequences of TMEM20 and SLC35E1, representing the "AMAC" and "SLC35C/E" subfamilies, are used as query against a set of 12 new model organisms (left column). Any shift in divergence time (from H. sapiens), compared to the corresponding organism in the (ordinal) set of model organisms (Methods), is indicated in the right hand column, with data from TimeTree [35].

Mentions: We extend the analysis to a new set of 12 species (9 new species, T. adhaerens, D. discoideum, and A. thaliana; see Figure 4), because a dozen species obviously represents a rather limited sampling of species, making our ability to resolve the time of emergence of any subfamily limited. We compared TimeTree divergence time data (measured from H. sapiens) for the new set of 12 species to the TimeTree divergence time data from the old set of 12 species (reporting the difference between the corresponding ordinal measurements in the right hand margin of Figure 4) [35].


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)

TBLASTN 2.2.24+ confirmatory search of oldest model organism sequence identified in subfamilies in edited EamA dendrogram. Using TBLASTN 2.2.24+, the human sequences of TMEM20 and SLC35E1, representing the "AMAC" and "SLC35C/E" subfamilies, are used as query against a set of 12 new model organisms (left column). Any shift in divergence time (from H. sapiens), compared to the corresponding organism in the (ordinal) set of model organisms (Methods), is indicated in the right hand column, with data from TimeTree [35].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: TBLASTN 2.2.24+ confirmatory search of oldest model organism sequence identified in subfamilies in edited EamA dendrogram. Using TBLASTN 2.2.24+, the human sequences of TMEM20 and SLC35E1, representing the "AMAC" and "SLC35C/E" subfamilies, are used as query against a set of 12 new model organisms (left column). Any shift in divergence time (from H. sapiens), compared to the corresponding organism in the (ordinal) set of model organisms (Methods), is indicated in the right hand column, with data from TimeTree [35].
Mentions: We extend the analysis to a new set of 12 species (9 new species, T. adhaerens, D. discoideum, and A. thaliana; see Figure 4), because a dozen species obviously represents a rather limited sampling of species, making our ability to resolve the time of emergence of any subfamily limited. We compared TimeTree divergence time data (measured from H. sapiens) for the new set of 12 species to the TimeTree divergence time data from the old set of 12 species (reporting the difference between the corresponding ordinal measurements in the right hand margin of Figure 4) [35].

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