Sequence of a highly divergent β tubulin gene reveals regional heterogeneity in the β tubulin polypeptide

The nucleotide sequence of a chicken genomic DNA segment containing the chicken β4 tubulin gene has been determined. The predicted amino acid sequence of β4 is surprisingly divergent from that of the chicken β2 gene that encodes the dominant neural β tubulin. β4 differs from β2 at 36 residue positions and encodes a polypeptide that is four amino acids longer, yielding a divergence of 8.9% between the two β tubulin isotypes. While many of the amino acid substitutions are conservative, several involve significant alteration in the physiochemical properties of the residue. Furthermore, the amino acid substitution positions are not randomly located within the primary sequence but are distinctly clustered: major divergence occurs in the carboxy-terminal region beyond residue 430 and within the second protein coding exon segments of the genes. In addition, large regions of absolute sequence conservation are also present. Certain sequences within the heterogeneous regions are conserved in other species, indicating that these regions are under positive evolutionary selection pressure and are therefore probably essential for some aspect of β-tubulin function. These findings strongly suggest that regional amino acid sequence heterogeneity may play an important role in the establishment of functionally differentiated β tubulin polypeptides.