title: Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters.
abstract: Slc22 family organic anion and cation transporters (OATs, OCTs, and OCTNs) are transmembrane proteins expressed predominantly in kidney and liver. These proteins mediate the uptake or excretion of numerous physiologically (and pharmacologically) important compounds, and accordingly have been the focus of intensive study. Here we investigate the molecular phylogeny of the slc22 transporters, identifying homologs in Drosophila and C. elegans, several of which are developmentally regulated, as well as reporting the cloning of a novel human family member, UST6, expressed exclusively in liver in both embryo and adult. The latter helps define a subfamily within the OATs, which appears to have human- and rodent-specific members, raising potential issues with respect to the use of rodents as models for the transport of organic anions (which include many pharmaceuticals) in humans. Although this phylogenetic inference could not be made on the basis of sequence alignment, analysis of intron phasing suggests that the OAT, OCT, and OCTN lineages of the slc22 family formed after the divergence of vertebrates and invertebrates. Subsequently, these lineages expanded through independent tandem duplications to produce multiple gene pairs. After analyzing over 200 other transporter genes, we find such pairing to be relatively specific to vertebrate organic anion and cation transporters, suggesting selection for gene pairing operating within this family in particular. This might reflect a requirement for redundancy or broader substrate specificity in vertebrates (compared to invertebrates), due to their greater physiological complexity and thus potentially broader exposure to organic ions.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California 92093-0693, USA.
authors.forename: Satish A
authors.initials: SA
authors.lastname: Eraly
authors.forename: Julio C
authors.initials: JC
authors.lastname: Monte
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Nigam
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D027361:Organic Anion Transporters / Q000145:classification / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000070590:Solute Carrier Proteins; D013045:Species Specificity
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C488773:SLC22A25 protein, human; D000070590:Solute Carrier Proteins