Over the past decade, our laboratory and others have been concerned with
molecular archaeological studies aimed at revealing the origins and
evolutionary histories of permeases (1). These studies have revealed
that several different families, defined on the basis of sequence
similarities, arose independently of each other, at different times in
evolutionary history, following different routes. When complete
microbial genomes first became available for analysis, we adapted p-
existing software and designed new programs that allowed us quickly to
identify probable transmembrane proteins, estimate their topologies and
determine the likelihood that they function in transport (2). This work
allowed us to expand previously-recognized families and to identify
dozens of new families. All of this work then led us to attempt to
design a rational but comprehensive classification system that would be
applicable to the complete complement of transport systems found in all
living organisms (3). The classification system that we have devised is
based primarily on mode of transport and energy coupling mechanism,
secondarily on molecular phylogeny, and lastly on the substrate
specificities of the individual permeases (4).