Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-IIb-perinatal-extraocular

Myosin heavy chain (MyHC) is the major contractile protein of muscle. We re port the first complete cosmid cloning and definitive physical map of the t andemly linked human skeletal MyHC genes at 17p13.1. The map provides new i nformation on the order, size, and relative spacing of the genes, and it re solves uncertainties about the two fastest twitch isoforms. The physical or der of the genes is demonstrated to contrast with the temporal order of the ir developmental expression. Furthermore, nucleotide sequence comparisons a llow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is pro vided for molecular analysis in patients with suspected primary skeletal my osinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.