Evolution of the cytoskeleton

Abstract

The eukaryotic cytoskeleton appears to have evolved from ancestral precursors related to prokaryotic FtsZ and MreB. FtsZ and MreB show 40-50% sequence identity across different bacterial and archaeal species. Here I suggest that this represents the limit of divergence that is consistent with maintaining their functions for cytokinesis and cell shape. Previous analyses have noted that tubulin and actin are highly conserved across eukaryotic species, but so divergent from their prokaryotic relatives as to be hardly recognizable from sequence comparisons. One suggestion for this extreme divergence of tubulin and actin is that it occurred as they evolved very different functions from FtsZ and MreB. I will present new arguments favoring this suggestion, and speculate on pathways. Moreover, the extreme conservation of tubulin and actin across eukaryotic species is not due to an intrinsic lack of variability, but is attributed to their acquisition of elaborate mechanisms for assembly dynamics and their interactions with multiple motor and binding proteins. A new structure-based sequence alignment identifies amino acids that are conserved from FtsZ to tubulins. The highly conserved amino acids are not those forming the subunit core or protofilament interface, but those involved in binding and hydrolysis of GTP.

Figure 1

Structure-based sequence alignment of FtsZ, α, β and γ tubulins. Amino acids judged to be highly conserved are indicated by grey shading, and are detailed in Table 1 and Fig. 2. The FtsZ sequences beyond G312 of the E. coli sequence are highly divergent even among FtsZs and show no relationship to tubulins.

Figure 2

The amino acids judged as highly conserved in Fig. 1 and Table 1 are shown in dark spacefilling on the structure of FtsZ from Pseudomonas aeruginosa(79) (PDB file 1OFU). GDP is white spacefill (mostly hidden). Several amino acids forming the GDP-binding pocket are indicated, but most are too close for separate identification. The figure was prepared with the program PyMol (DeLano Scientific LLC).