A millennial myosin census

Abstract

The past decade has seen a remarkable explosion in our knowledge of the size and diversity of the myosin superfamily. Since these actin-based motors are candidates to provide the molecular basis for many cellular movements, it is essential that motility researchers be aware of the complete set of myosins in a given organism. The availability of cDNA and/or draft genomic sequences from humans, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Dictyostelium discoideum has allowed us to tentatively define and compare the sets of myosin genes in these organisms. This analysis has also led to the identification of several putative myosin genes that may be of general interest. In humans, for example, we find a total of 40 known or predicted myosin genes including two new myosins-I, three new class II (conventional) myosins, a second member of the class III/ninaC myosins, a gene similar to the class XV deafness myosin, and a novel myosin sharing at most 33% identity with other members of the superfamily. These myosins are in addition to the recently discovered class XVI myosin with N-terminal ankyrin repeats and two human genes with similarity to the class XVIII PDZ-myosin from mouse. We briefly describe these newly recognized myosins and extend our previous phylogenetic analysis of the myosin superfamily to include a comparison of the complete or nearly complete inventories of myosin genes from several experimentally important organisms.

Figure 1

An unrooted phylogenetic tree of the myosin superfamily in humans. In this tree, solid lines indicate myosins known from cDNA sequences and dashed lines indicate putative myosins predicted from genomic sequence. Black dots represent nodes validated by bootstrapping values of >90%. Official HUGO human gene names (http://www.gene.ucl.ac.uk/nomenclature/) are indicated in bold, and synonymous names from human or related organisms such as rat (Myr) are indicated in plain type. Recently discovered or newly predicted myosin genes are italicized, and potential gene names suggested for myosins predicted from genomic sequence are indicated in brackets. Although all the myosin genes depicted in this figure are known to be present in humans, in a few cases sequence homologues from closely related organisms such as rat (myr1, myr4, myr6, and myr8) or mouse (Myo1f) were used to generate the tree. Sequences assembled from overlapping genomic clones or cDNAs are indicated in square brackets. This and the other trees illustrated here were generated from myosin head domain aa sequences essentially as described by Cheney et al. (1993). PH, pleckstrin homology; MyTH4, myosin tail homology 4; FERM, band four point one/ezrin/radixin/moesin. Note that the conventional myosin pseudogene is not included in the phylogenetic analysis due to incomplete head domain sequence. See text for specific references.

Figure 2

Bar diagrams of newly discovered or newly predicted myosins from humans and Drosophila. Dashed lines and light shading indicate expected structure of myosins predicted from partial genomic sequence. Dotted lines indicate uncertain N-terminal extensions predicted by Genscan. Glob., AF-6/dilute-class globular tail; Pro., proline-rich region. See text for details.

Figure 3

An unrooted phylogenetic tree of the myosin superfamily. A phylogenetic tree was assembled using myosin head domain protein sequences from all currently known or predicted myosins in humans, Drosophila, C. elegans, Dictyostelium, Arabidopsis, S. cerevisiae, and S. pombe, as well as selected myosins from other organisms. Species are identified by two or three letter abbreviations, and some gene names have been shortened to save space. Sequences predicted in full or in part from genomic clones are indicated by an asterisk. Bold type indicates orphan myosins that have not yet been assigned a class number. To minimize the introduction of gaps in the sequence alignment used to generate this tree, we increased the default CLUSTALX gap insertion penalty to 25 and the gap extension penalty to 0.5. Similar trees are available on the myosin home page (http://www.mrc-lmb.cam.ac.uk/myosin/myosin.html) and in recent papers (Soldati et al., 1999; Hodge and Cope, 2000; Sellers, 2000).

Figure 4

Organism-specific phylogenetic trees. Myosins present within a particular organism are highlighted against the comprehensive myosin tree from Figure 3. (A) Drosophila myosins. (B) C. elegans myosins. (C) Dictyostelium myosins. (D) Arabidopsis myosins.

Figure 5

Current myosin inventories and nomenclature for selected organisms. Classes are designated by the letter M (myosin) followed by Arabic numerals corresponding to the class number. Genes predicted in full or in part from genomic sequence are indicated by an asterisk. Accession numbers are for cDNA/protein sequences or genomic clones (in square brackets). It should be noted that the numbering of the budding yeast myosins (MYO1–5) and the unconventional myosins from C. elegans (HUM1–8; heavy chain of unconventional myosin) and rat (myr1–8; myosin from rat) corresponds to the order of discovery in these organisms and not their phylogenetic class. Drosophila myosins have traditionally been referred to by their chromosomal locus, Dictyostelium myosins are lettered (MyoA-MyoM), and Arabidopsis myosins were named ATM (class VIII) and MYA (class XI). The nomenclature of the vertebrate myosins-I is particularly confusing because the assigned human gene names do not correspond clearly to previous names. A table of vertebrate myosin-I homologues can be found in Supplemental Materials available online at www.molbiolcell.org. Chr., chromosome; Rn, Rattus norvegicus; Mm, Mus musculus; Hs, Homo sapiens.

Figure 6

Distribution of the myosin classes among selected organisms. As in Figure 5, the myosin classes are abbreviated with Arabic numerals corresponding to the class number. Asterisks denote that class XI myosins may be divergent members of a class V/XI superclass of putative organelle or particle transporters. Dicty, Dictyostelium.