New insights into myosin evolution and classification

Abstract

Myosins are eukaryotic actin-dependent molecular motors important for a broad range of functions like muscle contraction, vision, hearing, cell motility, and host cell invasion of apicomplexan parasites. Myosin heavy chains consist of distinct head, neck, and tail domains and have previously been categorized into 18 different classes based on phylogenetic analysis of their conserved heads. Here we describe a comprehensive phylogenetic examination of many previously unclassified myosins, with particular emphasis on sequences from apicomplexan and other chromalveolate protists including the model organism Toxoplasma, the malaria parasite Plasmodium, and the ciliate Tetrahymena. Using different phylogenetic inference methods and taking protein domain architectures, specific amino acid polymorphisms, and organismal distribution into account, we demonstrate a hitherto unrecognized common origin for ciliate and apicomplexan class XIV myosins. Our data also suggest common origins for some apicomplexan myosins and class VI, for classes II and XVIII, for classes XII and XV, and for some microsporidian myosins and class V, thereby reconciling evolutionary history and myosin structure in several cases and corroborating the common coevolution of myosin head, neck, and tail domains. Six novel myosin classes are established to accommodate sequences from chordate metazoans (class XIX), insects (class XX), kinetoplastids (class XXI), and apicomplexans and diatom algae (classes XXII, XXIII, and XXIV). These myosin (sub)classes include sequences with protein domains (FYVE, WW, UBA, ATS1-like, and WD40) previously unknown to be associated with myosin motors. Regarding the apicomplexan "myosome," we significantly update class XIV classification, propose a systematic naming convention, and discuss possible functions in these parasites.

Fig. 1.

Representative distance matrix-based phylogeny (protdist/neighbor) of myosin head domains. This tree is based on alignment 7 from a series of 12 alignments and corresponds to the most representative tree, as judged by the BS for select myosin classes (see Table 2 for details). The highly divergent class XVII myosins have been omitted from the main phylogeny, whereas the Inset (Upper Right) shows the respective part of a tree in which these myosins have been included (note the long branch connecting class XVII to the rest of the tree). BS support is based on analyses excluding rogue sequences (indicated by asterisk) and is indicated by circles only for select nodes in the tree. Fig. 3, which is published as supporting information on the PNAS web site, shows the same tree including all sequence names and BS values. (Lower) Domain structures for select myosins. “Myosin tail 2” refers to Pfam entry 06017 (TH1). Ac, Acanthamoeba castellanii; Cp, C. parvum; Dd, D. discoideum; Ec, E. cuniculi; My, Mizuhopecten yessoensis; Pb, Plasmodium berghei; Pf, P. falciparum; Py, P. yoelii; Tc, T. cruzi; Tpn, T. pseudonana; and Tt, T. thermophila.

Fig. 2.

Myosin class XIV phylogeny. This partial tree represents part of the phylogeny shown in Fig. 1. Note that sequences PfMyoE and PbMyoE had been omitted from the bootstrap analysis. ATS1 and MyTH4/FERM refer to myosin tail protein domains. Et, E. tenella; Gp, G. polymorpha; Bb, Babesia bovis; Ta, Theileria annulata; Tg, T. gondii; and Tp, Theileria parva.