Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: Implications for functional diversity

The conventional myosin motor proteins that drive mammalian skeletal and ca rdiac muscle contraction include eight sarcomeric myosin heavy chain (MyHC) isoforms. Six skeletal MyHCs are encoded by genes found in tightly linked clusters on human and mouse chromosomes 17 and 11, respectively. The full c oding regions of only two out of six mammalian skeletal MyHCs had been sequ enced prior to this work. In an effort to assess the extent of sequence div ersity within the human MyHC family we present new full-length coding seque nces corresponding to four additional human genes: MyHC-IIb, MyHC-extraocul ar, MyHC-IIa and MyHC-IIx/d. This represents the first opportunity to compa re the full coding sequences of all eight sarcomeric MyHC isoforms within a vertebrate organism. Sequence variability has been analyzed in the context of available structure/function data with an emphasis on potential functio nal diversity within the family. Results indicate that functional diversity among MyHCs is likely to be accomplished by having small pockets of sequen ce diversity in an otherwise highly conserved molecule. (C) 1999 Academic P ress.