A hypothesis on the origin and evolution of tubulin

Int Rev Cell Mol Biol. 2013;302:41-185. doi: 10.1016/B978-0-12-407699-0.00002-9.


Tubulin, the protein subunit of microtubules (MTs), is an α/β heterodimer. In this chapter, a hypothesis on the evolution of the tubulin molecule is proposed, based in part on recent reports on the structures and functions of different forms of tubulin and its relatives. The concentration is on three main areas. 1) Evolution of the vertebrate β-tubulin isotypes. In addition to providing a clear idea about the relationships among these isotypes, recent data suggest that tubulin may have functions that do not involve being in a MT, namely, that it can function as an isolated α/β dimer or as a non-MT polymer. 2) Examination of the entire tubulin superfamily, which includes not only tubulins α, β, γ, δ, ε, η, and others but also a variety of prokaryotic proteins. The hypothesis is presented that the common ancestor of all these proteins formed a filamentous curving polymer that used the energy of GTP hydrolysis to apply force to nucleic acids and/or membranes and that this common ancestor may have been coeval with the first cells. A variety of chaperones, motors and MT-associated proteins may have coevolved with tubulin and their histories illuminate that of tubulin. The branched, highly negatively charged C-terminal domain present on α- and β-tubulin appears to be a relatively recent addition to tubulin. 3) The hypothesis is presented that the C-terminal domain may have been of prebiotic origin and that it gradually developed into a protein serving particular metabolic functions whose gene eventually became fused with those of α- and β-tubulin. Finally, some experiments are proposed that could illuminate the probability of these hypotheses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Eukaryotic Cells / metabolism
  • Evolution, Molecular*
  • Microtubules / genetics
  • Microtubules / metabolism
  • Prokaryotic Cells / metabolism
  • Protein Multimerization / physiology*
  • Tubulin / genetics*
  • Tubulin / metabolism*


  • Tubulin