Stepwise evolution of the centriole-assembly pathway

Abstract

SummaryThe centriole and basal body (CBB) structure nucleates cilia and flagella, and is an essential component of the centrosome, underlying eukaryotic microtubule-based motility, cell division and polarity. In recent years, components of the CBB-assembly machinery have been identified, but little is known about their regulation and evolution. Given the diversity of cellular contexts encountered in eukaryotes, but the remarkable conservation of CBB morphology, we asked whether general mechanistic principles could explain CBB assembly. We analysed the distribution of each component of the human CBB-assembly machinery across eukaryotes as a strategy to generate testable hypotheses. We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs. Unexpectedly, other players (SAK/PLK4, SPD2/CEP192 and CP110) emerged in a taxon-specific manner. We report that gene duplication plays an important role in the evolution of CBB components and show that, in the case of BLD10/CEP135, this is a source of tissue specificity in CBB and flagella biogenesis. Moreover, we observe extreme protein divergence amongst CBB components and show experimentally that there is loss of cross-species complementation among SAK/PLK4 family members, suggesting species-specific adaptations in CBB assembly. We propose that the UNIMOD theory explains the conservation of CBB architecture and that taxon-and tissue-specific molecular innovations, gained through emergence, duplication and divergence, play important roles in coordinating CBB biogenesis and function in different cellular contexts. Journal of Cell ScienceTo investigate the existence of such a universal CBB-assembly mechanism, we searched for homologs of known CBB-assembly proteins in a set of 26 representative eukaryotic species, covering the crown eukaryotic groups and representing the diversity of function and architecture (including absence) of CBBs ( Fig. 2A,B; see supplementary material Tables S1 and S2). We calculated the correlation between the presence of each molecule and the presence of the CBB, using a normalized Hamming distance (Fig. 2). Given the poor annotation of the proteomes of certain species and the absence of structural information regarding the existence of a CBB in others, we arbitrarily defined that the presence of a molecule and the occurrence of the CBB structure were correlated if this occurred in at least 80% of the species (Fig. 2). To our surprise, given the conservation of the CBB structure, only a subset of CBBassembly proteins obey the criteria above defined: SAS4/CPAP, SAS6 and BLD10/CEP135 (Fig. 2). This evolutionarily cohesive behavior suggests that these three molecules are part of the same functional ancestral module in CBB assembly, which, for simplicity, we will call UNIversal MODule (UNIMOD). Amongst the six studied families, the UNIMOD components are, in fact, the only ones required to define the CBB architecture: SAS...

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