Lampreys Have a Single Gene Cluster for the Fast Skeletal Myosin Heavy Chain Gene Family

Muscle tissues contain the most classic sarcomeric myosin, called myosin II, which consists of 2 heavy chains (MYHs) and 4 light chains. In the case of humans (tetrapod), a total of 6 fast skeletal-type MYH genes ( MYH s) are clustered on a single chromosome. In contrast, torafugu (teleost) contains at least 13 fast skeletal MYH s, which are distributed in 5 genomic regions; the MYH s are clustered in 3 of these regions. In the present study, the evolutionary relationship among fast skeletal MYH s is elucidated by comparing the MYH s of teleosts and tetrapods with those of cyclostome lampreys, one of two groups of extant jawless vertebrates (agnathans). We found that lampreys contain at least 3 fast skeletal MYH s, which are clustered in a head-to-tail manner in a single genomic region. Although there was apparent synteny in the corresponding MYH cluster regions between lampreys and tetrapods, phylogenetic analysis indicated that lamprey and tetrapod MYH s have independently duplicated and diversified. Subsequent transgenic approaches showed that the 5′-flanking sequences of Japanese lamprey fast skeletal MYH s function as a regulatory sequence to drive specific reporter gene expression in the fast skeletal muscle of zebrafish embryos. Although zebrafish MYH promoters showed apparent activity to direct reporter gene expression in myogenic cells derived from mice, promoters from Japanese lamprey MYH s had no activity. These results suggest that the muscle-specific regulatory mechanisms are partially conserved between teleosts and tetrapods but not between cyclostomes and tetrapods, despite the conserved synteny.