Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved

Abstract

Myosin heavy chains (MyHCs) are highly conserved ubiquitous actin-based motor proteins that drive a wide range of motile processes in eukaryotic cells. MyHC isoforms expressed in skeletal muscles are encoded by a multigene family that is clustered on syntenic regions of human and mouse chromosomes 17 and 11, respectively. In an effort to gain a better understanding of the genomic organization of the skeletal MyHC genes and its effects on the regulation, function, and molecular genetics of this multigene family, we have constructed high-resolution physical maps of both human and mouse loci using PCR-based marker content mapping of P1-artificial chromosome clones. Genes encoding six MyHC isoforms have been mapped with respect to their linear order and transcriptional orientations within a 350-kb region in both human and mouse. These maps reveal that the order, transcriptional orientation, and relative intergenic distances of these genes are remarkably conserved between these species. Unlike many clustered gene families, this order does not reflect the known temporal expression patterns of these genes. However, the conservation of gene organization since the estimated divergence of these species (approximately 75-110 million years ago) suggests that the physical organization of these genes may be significant for their regulation and function.

Figure 1

Physical maps of skeletal MyHC gene clusters. The top line in each map shows the order of markers (listed in Table 1) established by STS content mapping of PACs aligned below. PAC names and sizes (if determined) are indicated at the left and right ends of PACs, respectively. MyHC genes identified in end rescue sequences (hatched symbols) are indicated below symbol. Spacing of markers does not reflect actual scale.

Figure 2

Conservation of human and mouse skeletal MyHC gene organization. Closed arrows indicate transcriptional orientation determined for human and mouse genes. Open arrow indicates transcriptional orientation determined for mouse only. Intergenic distances as determined by long range PCR are 1, 4.5 kb (for human and mouse) between MyHC-IIa and MyHC-IIx/d, and 2, 9.0 kb (human) and 5.0 kb (mouse) between MyHC-IIx/d and MyHC-IIb. Unlabeled intergenic distances are estimated to be ≈15–60 kb. Each gene cluster spans at least 350 kb.