(last modified on March 18, 2001)
Many biological problems of the vertebrates have benefited from complementary studies which exploit the experimental amenability and genetic simplicity of invertebrate organisms. The muscular dystrophies are no exception.
The recognition that all vertebrates seem to have well-defined sequences encoding dystrophin, utrophin and DRP2 (Roberts et al., 1996) stimulated a search for ancestral sequences in invertebrates. Perhaps unsurprisingly, given the high degree of conservation of the vertebrate proteins, recognisable dystrophin-like sequences were identified in sea urchin (Wang et al., 1998) and in amphioxus, sea squirt, starfish, scallop, fruit fly and nematode (Roberts & Bobrow, 1998).
In each case, phylogenetic analysis showed the invertebrate dystrophins to be orthologues of the last common ancestor of dystrophin, utrophin and DRP2. Thus, as with many other protein families, the radiation of the vertebrates is marked by multiple duplication of the single ancestral gene. It was also found that, at least for sea urchin (Wang et al., 1998), nematode (Bessou et al., 1998) and fruit fly (Greener & Roberts, 2000), the ancestral protein more resembles the giant rod-like proteins dystrophin and utrophin than the shorter DRP2.
Given the diversity of the remainder of the components of the vertebrate dystrophin complex, how much simpler is its invertebrate counterpart ? The release of the more-or-less complete sequence of the Drosophila genome has afforded the opportunity to assess the invertebrate repertoire of dystrophin complex components, using a combination of in vitro and in silico techniques (Greener & Roberts, 2000).
The basic findings are summarised below:
|Gene (symbol)||cDNA sequence||Genomic sequence||Protein sequence|
|dystrophin / utrophin / DRP2 orthologue (DYS)
|AC008192 + AC007815||AAG17395|
|alpha/beta-like syntrophin (SYN1)||AF277388||AAG17397|
|gamma-like syntrophin (SYN2)||AF277389||AAG17398|
|alpha- and epsilon-sarcoglycan (SCG-alpha/epsilon)||AF277391||AAG17400|
|gamma- and delta-sarcoglycan (SCG-gamma/delta)||AF277393||AAG17402|
| Top of page | Dystrophin-associated
Glycoprotein Complex |
| LMDp homepage |