Evolution of modular intraflagellar transport from a coatomer-like progenitor

Abstract

The intraflagellar transport (IFT) complex is an integral component of the cilium, a quintessential organelle of the eukaryotic cell. The IFT system consists of three subcomplexes [i.e., intraflagellar transport (IFT)-A, IFT-B, and the BBSome], which together transport proteins and other molecules along the cilium. IFT dysfunction results in diseases collectively called ciliopathies. It has been proposed that the IFT complexes originated from vesicle coats similar to coat protein complex (COP) I, COPII, and clathrin. Here we provide phylogenetic evidence for common ancestry of IFT subunits and α, β', and ε subunits of COPI, and trace the origins of the IFT-A, IFT-B, and the BBSome subcomplexes. We find that IFT-A and the BBSome likely arose from an IFT-B-like complex by intracomplex subunit duplication. The distribution of IFT proteins across eukaryotes identifies the BBSome as a frequently lost, modular component of the IFT. Significantly, loss of the BBSome from a taxon is a frequent precursor to complete cilium loss in related taxa. Given the inferred late origin of the BBSome in cilium evolution and its frequent loss, the IFT complex behaves as a "last-in, first-out" system. The protocoatomer origin of the IFT complex corroborates involvement of IFT components in vesicle transport. Expansion of IFT subunits by duplication and their subsequent independent loss supports the idea of modularity and structural independence of the IFT subcomplexes.

Fig. 1.

Phylogenetic analyses of the ε-IFT subunits and IFT complex composition. (A) Composition of the IFT subcomplexes. Blue, αβ-IFT subunits with domain structures similar to COPI-α and -β′; yellow, ε-IFT subunits with domain structures similar to COPI-ε; red, small GTPases; green, putative β-propeller BBS subunits; white, subunits that are not homologous to other subunits. Positions of the subunits do not reflect their actual positions within the IFT complex. (B) Phylogenetic tree of ε-IFT subunits. (C) Evolutionary scenario for the origin of IFT-A, IFT-B, and BBSome subcomplexes, based on B.

Fig. 2.

Multiple sequence alignment of the αβ-IFT conserved region extracted from the full alignment. The full alignment contains 52 sequences. Larger inserts have been removed and are represented by number of residues removed between parentheses. An overview of the whole alignment is shown in Fig. S1.

Fig. 3.

Coulson plot demonstrating presence and absence (or loss) of IFT subunits in 52 eukaryotic genomes. Complexes are divided into IFT-A and -B and BBSome (rows), and taxa are displayed as columns. Super groups are color-coded for clarity, and phylogenetic relationships are shown at the top schematically. The presence of a cilium is also shown in the top row (black).

Fig. 4.

Predicted fold types present within the IFT and BBSome subunits in H. sapiens and T. brucei. (A) ε-IFT subunits (yellow in Fig. 1A), (B) αβ-IFT subunits (blue in Fig. 1A), and (C) BBSome subunits (green in Fig 1A). The β-propeller fold is indicated in blue, the TPR/α-solenoid-like fold in green, a disordered region in pink, and a coiled coil in cyan.

Fig. 5.

Predicted origin and subsequent loss of each IFT subcomplex based on the phylogenetic trees for the COP-α–, COP-β′–, and COP-ε–like IFT subunits, as well as the presence/absence profiles of individual subunits. As a result of the absence of BBSome subunits in the αβ-like IFT phylogenetic tree, it is uncertain whether IFT-A or BBSome emerged as the second IFT subcomplex. The last common eukaryotic ancestor (LECA) already contained the complete set of IFT subunits observed in C. reinhardtii, Leishmania major, and humans, and this must have evolved in the transition between the last common eukaryotic ancestor and the first common eukaryotic ancestor (FECA). Species related to nonciliated species have lost the BBSome and, in one case, have also lost IFT-A.