The ABC Transporter Gene Family of Caenorhabditis elegans Has Implications for the Evolutionary Dynamics of Multidrug Resistance in Eukaryotes

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 atlower concentrations in cells than in their environment. Multi-drug resistance (MDR), oftenmediated 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, amongwhich the ABC transporters are the largest. The number of candidate MDR genes means that studyof the drug-resistance properties of an organism cannot be effectively carried out without taking agenomic perspective.Results: We have annotated sequences for all 60 ABC transporters from the Caenorhabditiselegans 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 unifiednomenclature is presented. Comparison between genomes reveals much gene duplication and loss,and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR arefound 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 'dynamiccoherence'.This is an unusual result for such a highly conserved gene family as this one, present inall domains of cellular life. Mechanistically, this may result from the broad substrate specificity ofsome ABC proteins, which both reduces selection against gene loss, and leads to the facile sortingof functions among paralogs following gene duplication.