Stability of Na⁺-K⁺-ATPase α-subunit isoforms in evolution

Encoding DNA for α₂- and α₃-isoforms of the α-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 α-subunit isoforms make possible an assessment of α-subunit isoform diversity among vertebrates. There is approximately twice as much amino acid sequence difference between α-isoforms within a single species as there is difference between corresponding α-isoforms of bird and mammal. These data are consistent with triplication of the α-subunit gene and evolution of substantially different α-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 conservation of isoform-specific structural features are discussed in terms of transport functions and bioregulation of the Na⁺-K⁺-ATPase.