Abstract
Here we show a complete list of the P-type ATPase genes in Caenorhabditis elegans and Drosophila melanogaster. A detailed comparison of the deduced amino-acid sequences in combination with phylogenetic and chromosomal analyses has revealed the following: (1) The diversity of this gene family has been achieved by two major evolutionary steps; the establishment of the major P-type ATPase subgroups with distinct substrate (ion) specificities in a common ancestor of vertebrate and invertebrate, followed by the evolution of multiple isoforms occurring independently in vertebrate and invertebrate phyla. (2) Pairs of genes that have intimate phylogenetic relationship are frequently found in proximity on the same chromosome. (3) Some of the Na,K- and H,K-ATPase isoforms in D. melanogaster and C. elegans lack motifs shown to be important for alpha/beta-subunit assembly, suggesting that such alpha- and beta-subunits might exist by themselves (lonely subunits). The mutation rates for these subunits are much faster than those for the subunits with recognizable assembly domains. (4) The lonely alpha-subunits also lack the major site for ouabain binding that apparently arose before the separation of vertebrates and invertebrates and thus well before the separation of vertebrate Na,K-ATPases and H,K-ATPases. These findings support the idea that a relaxation of functional constraints would increase the rate of evolution and provide clues for identifying the origins of inhibitor sensitivity, subunit assembly, and separation of Na,K- and H,K-ATPases.
