Identification of conserved isotype-defining variable region sequences for four vertebrate β tubulin polypeptide classes

We report the determination of the complete sequences for two chicken β tubulin genes, β3 and β5. Taken with the previously published efforts, we have determined the primary structures of five of the seven β tubulin genes in this vertebrate species. A comparison of these sequences unambiguously reveals that amino acid sequence variations among different β tubulin gene products are distinctly clustered within an otherwises highly conserved framework of the β tubulin molecule. To determine the extent to which this pattern of structural heterogeneity is conserved among vertebrates, we have isolated novel β tubulin sequences from human and mouse cDNA libraries and compared these and all other known vertebrate β tubulin sequences with the family of chicken polypeptide sequences. What emerges from such comparison is the recognition of distinct, evolutionarily conserved isotypes of β tubulin that are distinguished primarily by their characteristic carboxyl-terminal variable region sequence and, to a lesser extent, by sequence in an amino-terminal variable domain as well. These correlations represent a convincing demonstration that multiple β tubulin genes in vertebrates encode a family of closely related but structurally distinct β tubulin isotypes and further serve to define the sequences of four classes of polypeptide isotypes that constitute that family.