Stability of Na(+)-K(+)-ATPase alpha-subunit isoforms in evolution

K. Takeyasu, V. Lemas and D. M. Fambrough Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908. Encoding DNA for alpha 2- and alpha 3-isoforms of the alpha-subunit of the chicken Na(+)-K(+)-ATPase have been cloned, and their nucleotide sequences and deduced amino acid sequences are reported. Comparisons between these data and comparable data for the rat alpha-subunit isoforms make possible an assessment of alpha-subunit isoform diversity among vertebrates. There is approximately twice as much amino acid sequence difference between alpha-isoforms within a single species as there is difference between corresponding alpha-isoforms of bird and mammal. These data are consistent with triplication of the alpha-subunit gene and evolution of substantially different alpha-subunit isoforms before the separation of avian and mammalian lineages over 200 million years ago and then retention of the majority of these structural differences through subsequent evolution. The implications of this conversation of isoform-specific structural features are discussed in terms of transport functions and bioregulation of the Na(+)-K(+)-ATPase.