SEQUENCE RELATIONSHIPS BETWEEN INTEGRAL INNER MEMBRANE-PROTEINS OF BINDING PROTEIN-DEPENDENT TRANSPORT-SYSTEMS - EVOLUTION BY RECURRENT GENE DUPLICATIONS

Periplasmic binding protein-dependent transport systems are composed o f a periplasmic substrate-binding protein, a set of 2 (sometimes 1) ve ry hydrophobic integral membrane proteins, and 1 (sometimes 2) hydroph ilic peripheral membrane protein that binds and hydrolyzes ATP. These systems are members of the superfamily of ABC transporters. We perform ed a molecular phylogenetic analysis of the sequences of 70 hydrophobi c membrane proteins of these transport systems in order to investigate their evolutionary history. Proteins were grouped into 8 clusters. Wi thin each cluster, protein sequences displayed significant similaritie s, suggesting that they derive from a common ancestor. Most clusters c ontained proteins from systems transporting analogous substrates such as monosaccharides, oligopeptides, or hydrophobic amino acids, but thi s was not a general rule. Proteins from diverse bacteria are found wit hin each cluster, suggesting that the ancestors of current clusters we re present before the divergence of bacterial groups. The phylogenetic trees computed for hydrophobic membrane proteins of these permeases a re similar to those described for the periplasmic substrate-binding pr oteins. This result suggests that the genetic regions encoding binding protein-dependent permeases evolved as whole units. Based on the resu lts of the classification of the proteins and on the reconstructed phy logenetic trees, we propose an evolutionary scheme for periplasmic per meases. According to this model, it is probable that these transport s ystems derive from an ancestral system having only 1 hydrophobic membr ane protein. None of the proteins considered in this study display det ectable sequence similarity to hydrophobic membrane proteins or domain s from other ABC transporters such as bacterial polysaccharide export systems, bacterial toxin proteins exporters, and eukaryotic ABC protei ns. It is likely that they constitute a specific subfamily within the superfamily of ABC transporters.