RELATIONSHIPS BETWEEN BACTERIAL DRUG-RESISTANCE PUMPS AND OTHER TRANSPORT PROTEINS

We have used three reference sequences representative of bacterial dru g resistance pumps and sugar transport proteins to collect the 91 most closely related sequences from a composite, nonredundant protein sequ ence database. Having eliminated certain very close relatives, the rem ainder were subjected to analysis and alignment by using two different similarity matrices: one of these was a matrix based on structural co nservation of amino acid residues in proteins of known conformation an d the other was based on the more familiar mutational matrix. Unrooted similarity trees for these proteins were constructed for each matrix and compared. A systematic analysis of the differences between these t rees was undertaken and the sequences were analyzed for the presence o r absence of certain sequence motifs. The results show that the clades created by the two methods are broadly comparable but that there are some clusters of sequences that are significantly different. Further a nalysis confirmed that (1) the sequences collected by this objective m ethod are all known or putative 12-helix (in some cases reported as 14 -helix) transmembrane proteins, (2) there is evidence for few cases of an origin based on gene duplication, (3) the bacterial drug resistanc e pumps are distributed in more than one clade and cannot be regarded as a definitive subset of these proteins, and that (4) the diversity i s such that there is no evidence of a single ancestral protein. The po ssible extension of the methods to other cases of divergent protein se quences is discussed.