The microtubule skeleton and the evolution of neuronal complexity in vertebrates.

The evolution of a highly developed nervous system is mirrored by the ability of individual neurons to develop increased morphological complexity. As microtubules (MTs) are crucially involved in neuronal development, we tested the hypothesis that the evolution of complexity is driven by an increasing capacity of the MT system for regulated molecular interactions as it may be implemented by a higher number of molecular players and a greater ability of the individual molecules to interact. We performed bioinformatics analysis on different classes of components of the vertebrate neuronal MT cytoskeleton. We show that the number of orthologs of tubulin structure proteins, MT-binding proteins and tubulin-sequestering proteins expanded during vertebrate evolution. We observed that protein diversity of MT-binding and tubulin-sequestering proteins increased by alternative splicing. In addition, we found that regions of the MT-binding protein tau and MAP6 displayed a clear increase in disorder extent during evolution. The data provide evidence that vertebrate evolution is paralleled by gene expansions, changes in alternative splicing and evolution of coding sequences of components of the MT system. The results suggest that in particular evolutionary changes in tubulin-structure proteins, MT-binding proteins and tubulin-sequestering proteins were prominent drivers for the development of increased neuronal complexity.