Project abstract for group titusmeg

Molecular Evolution of MyTH-FERM Myosins

Cell motility, the movement of cells through their environment, is of fundamental importance in biology and particularly in multicellular animals as cells must migrate through the devleoping organism to form specialized tissues. The Titus group studies myosins, a class of motor proteins with deep evolutionary roots that control cell shape, motility, and migration in both animals and Dictyostelium (Dicty), a social amoeba. Dicty is a unicellular organism that feeds on soil bacteria and develops into a multicellular aggregate, and is a model for cell motility and migration. These researchers have identified two MyTH4-FERM (MF) myosins in Dicty. MF myosins contain both a motor and a binding module, the MyTH4-FERM domain, allowing the motor to generate force across the cytoskeleton and receptors at the cell membrane. MF myosins are a diverse family of motors found throughout the eukaryotic tree of life. Interestingly, MF myosins are nearly always found to play roles in formation of large actin-filament structures including gut microvilli (myosin 7b), stereocilia of the ear (myosin 15), and filopodia of epithelial cells and neurons (myosin 10). This group has shown that Dicty myosin 7 generates filopodia by a mechanism strikingly similar to myosin 10 in humans. The similar functions of MF myosins suggests a shared ancestral function may have been conserved despite extensive gene duplication, a poorly understood aspect of evolution. Another Dicty MF myosin, myosin 44, has an essential role in chemotactic cell migration. In contrast to myosin 7, animals do not possess a homolog to myosin 44 despite common mechanisms of cell migration. Research in this lab uses computational phylogenetic methods to trace the evolution of the MyTH4-FERM myosin gene family. In the case of Dicty myosin 7, ancestral functions appear to have been conserved and diversified during evolution while in the case of myosin 44 it appears that a new function has evolved in the social amoeba. Phylogenetic analysis allows the group to use the MF myosins as a test case for how ancestral functions may be either conserved or lost as new functions emerge in a gene family.

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