ISOLATION OF SEVERAL HUMAN AXONEMAL DYNEIN HEAVY-CHAIN GENES - GENOMIC STRUCTURE OF THE CATALYTIC SITE, PHYLOGENETIC ANALYSIS AND CHROMOSOMAL ASSIGNMENT

Dynein heavy chains (DHCs) are the main components of multisubunit mot or ATPase complexes called dyneins, Axonemal dyneins provide the drivi ng force for ciliary and flagellar motility. Recent molecular studies demonstrated that multiple DHC isoforms are produced by separate genes . We describe the isolation of five human axonemal DHC genes. Analysis of the human genomic clones revealed the existence of intronic sequen ces that were used to demonstrate that human axonemal DHC genes are lo cated on different chromosomes, The cloned human DHC sequences were in tegrated into an evolutionary approach based on phylogenetic analysis. Tissue expression studies showed that these human axonemal DHCs are e xpressed in testis and/or trachea, two tissues with axonemal structure s that can be altered in primary ciliary dyskinesia, making DHC genes strong candidates in the genesis of these human diseases. (C) 1997 Fed eration of European Biochemical Societies.