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The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes.

Sheps JA, Ralph S, Zhao Z, Baillie DL, Ling V - Genome Biol. (2004)

Bottom Line: Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times.This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life.Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.

View Article: PubMed Central - HTML - PubMed

Affiliation: British Columbia Cancer Research Centre, BC Cancer Agency, 601 West 10th Avenue, Vancouver, BC, V5Z 1L6 Canada.

ABSTRACT

Background: Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective.

Results: We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times.

Conclusions: ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.

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Phylogenetic trees of ABCD, ABCE, and ABCF proteins in four eukaryote genomes. Phylogenies derived and displayed according to the procedure outlined in the legend of Figure 3.
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Figure 6: Phylogenetic trees of ABCD, ABCE, and ABCF proteins in four eukaryote genomes. Phylogenies derived and displayed according to the procedure outlined in the legend of Figure 3.

Mentions: Thirty ABC transporters are described in the yeast genome, or approximately 0.5% of its approximately 6,000 proteins [13]. At present 49 human ABC transporters have been identified and, at least partially, cloned. They are included here (Figures 3,4,5,6,7 and Table 2) to illustrate their relationships with nematode proteins, which might then shed light on their biological roles. Inclusion of human as well as D. melanogaster ABC transporters in our tree allows us to explicitly classify C. elegans ABC transporters according to the current eight-subfamily taxonomic scheme for ABC transporters [12].


The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes.

Sheps JA, Ralph S, Zhao Z, Baillie DL, Ling V - Genome Biol. (2004)

Phylogenetic trees of ABCD, ABCE, and ABCF proteins in four eukaryote genomes. Phylogenies derived and displayed according to the procedure outlined in the legend of Figure 3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC395765&req=5

Figure 6: Phylogenetic trees of ABCD, ABCE, and ABCF proteins in four eukaryote genomes. Phylogenies derived and displayed according to the procedure outlined in the legend of Figure 3.
Mentions: Thirty ABC transporters are described in the yeast genome, or approximately 0.5% of its approximately 6,000 proteins [13]. At present 49 human ABC transporters have been identified and, at least partially, cloned. They are included here (Figures 3,4,5,6,7 and Table 2) to illustrate their relationships with nematode proteins, which might then shed light on their biological roles. Inclusion of human as well as D. melanogaster ABC transporters in our tree allows us to explicitly classify C. elegans ABC transporters according to the current eight-subfamily taxonomic scheme for ABC transporters [12].

Bottom Line: Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times.This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life.Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.

View Article: PubMed Central - HTML - PubMed

Affiliation: British Columbia Cancer Research Centre, BC Cancer Agency, 601 West 10th Avenue, Vancouver, BC, V5Z 1L6 Canada.

ABSTRACT

Background: Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective.

Results: We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times.

Conclusions: ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication.

Show MeSH
Related in: MedlinePlus