The genes of Na,K-ATPase, a selfreview.

The review is devoted to analysis of research carried out in the author's laboratory on structure-function relationships in genes coding for Na,K-ATPases. Also considered are problems related to molecular evolution of ion-transporting ATPases. This brief review is devoted to a fragment of research carried out in my laboratory, the Laboratory of Human Genes Structure and Function at the Shemyakin Institute of Bioorganic Chemistry, USSR Academy of Sciences. The area of the review may be named as structural-evolutionary analysis of functional anatomies of genes. The approach is fairly standard and its essence was formulated long ago: evolution decides 'to be or not to be' based on usefulness or lack of it. The elements of genes that are important for the gene function are retained in the course of evolution, and a comparison of genes having similar functions in different species should, hopefully, reveal different behavior of gene blocks, conservation of functionally significant blocks and variability of less significant or insignificant ones. An approach like this has been widely used in comparing proteins. However, a study of genes gives the investigator yet another tool of structural and evolutionary import: the exon structure may be relevant to the gene's evolutionary history, with exons corresponding to the functional domains (arguments for and against this fascinating hypothesis have been reviewed by Blake (Blake, 1985). However, even if the exon-domain correlation does not hold in the general case, a similarity in the exon-intron pattern of genes from different species is indicative of their common evolutionary origin and is enforcing the logic of variability analysis, provided, of course, that the compared genes have a common predecessor. A few years ago we employed this approach to analyze the functional structure of genes coding for subunits of bacterial DNA-dependent RNA polymerases and constructed functional maps of the enzyme. After that, a similar study of Na,K-ATPase genes to be reviewed here was started. The entire project became possible through collaboration with the lab of Dr. N. N. Modyanov, an eminent specialist in protein chemistry who had already accumulated considerable information on Na,K-ATPase from pig kidneys by that time. I would also like to stress that the work has been started on the initiative of the deceased Director of the Institute, Yu. A. Ovchinnikov. Since this is a self-review, I am asking my colleagues whose work will not be cited here to excuse me.(ABSTRACT TRUNCATED AT 400 WORDS)