Chapter 3 How Did the Cilium Evolve?

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Abstract

The cilium is a characteristic organelle of eukaryotes constructed from over 600 proteins. Bacterial flagella are entirely different. 9 + 2 motile cilia evolved before the divergence of the last eukaryotic common ancestor (LECA). This chapter explores, compares, and contrasts two potential pathways of evolution: (1) via invasion of a centriolar-like virus and (2) via autogenous formation from a pre-existing microtubule-organizing center (MTOC). In either case, the intraflagellar transport (IFT) machinery that is nearly universally required for the assembly and maintenance of cilia derived from the evolving intracellular vesicular transport system. The sensory function of cilia evolved first and the ciliary axoneme evolved gradually with ciliary motility, an important selection mechanism, as one of the driving forces.

Introduction

In this chapter, we explore the evolution of one of the most characteristic organelles of the eukaryotic cell, the cilium. Cilia, sometimes called flagella in the literature, are found exclusively on eukaryotic cells, throughout the protista, in many plant phyla on gametes, and on somatic cells and/or gametes in virtually every metazoan phylum. (Bacterial flagella are entirely different organelles.) In humans, motile cilia are present on nasal and tracheal lining cells, ependymal cells of the brain, and cells lining the oviduct. The sperm tail is a cilium with accessory elements. The sensory hair cells of the ear and semicircular canals possess a single “kinocilium” (the “stereocilia” of the ear and epididymis are microvilli, not cilia). Olfactory sense cells each possess multiple cilia, which may be immotile. During embryogenesis, motile cilia present at the node during gastrulation evidently initiate the determination of left–right body asymmetry. In addition, many cells in the body possess a single nonmotile cilium called a primary cilium; a primary cilium with extensive membrane modifications forms the outer segment of the ciliary photoreceptors of the vertebrate eye. A current review of the structure and function of motile and primary mammalian cilia is found in Satir and Christensen (2007).

A series of combined genomic–proteomic studies on protistan (Chlamydomonas, Tetrahymena) motile cilia, invertebrate (primarily Caenorhabditis elegans) sensory cilia, and mammalian and human cilia reveal that cilia are comprised of upwards of 600 proteins (Avidor-Reiss et al., 2004, Li et al., 2004, Ostrowski et al., 2002, Pazour et al., 2005, Scholey, 2003, Smith et al., 2005). Many or most of the genes related to cilia are missing in genomes of nonciliated organisms, such as Arabidopsis. When cilia are present, a remarkable portion of the nuclear genome, perhaps 3–5% of the typical genome, is devoted to this single organelle. The proteins produced by these genes are highly conserved. Three well-studied illustrative examples of proteins equally important in the single-celled alga Chlamydomonas reinhardtii and man are (1) axonemal dyneins, for example, OADα (the α-subunit of outer arm dynein) (Wilkes et al., 2008); (2) hydin (Lechtreck et al., 2008), a central pair projection; and (3) polaris or IFT88, a component of the intraflagellar transport (IFT) system (Pazour et al., 2000, Yoder et al., 2002).

Proteins such as these form defined parts of complex structures in the cilium. As has been understood for over half a century, almost all motile cilia are built on a similar plan, a 200 nm diameter cytoskeletal bundle of nine peripheral doublet microtubules surrounding a central singlet pair, the so-called 9 + 2 axoneme, which grows from a basal body and is enclosed in an extension of the cell membrane called the ciliary membrane (Fig. 3.1). The ciliary membrane incorporates specialized receptors and channels and confers on all cilia a sensory function, the ability to respond to external molecular signals (Christensen et al., 2007). The basal body itself is almost universally an arrangement of nine triplet microtubules, essentially identical to a centriole that has become attached to the cell membrane and formed a specialized structure called the ciliary necklace (Gilula and Satir, 1972). The cilium grows beyond the necklace with each of the nine triplet microtubules reduced to an axonemal doublet. In the transition zone, the central pair arises. Growth to lengths often greater than 10 μm occurs, again almost universally, by a process discovered more recently that has been named intraflagellar transport (Blacque et al., 2008, Rosenbaum and Witman, 2002, Scholey, 2003).

The motile cilium is a nanomachine powered by molecular motors, the axonemal dyneins attached to one edge of each axonemal doublet. The ATPase activity of the OADs and IADs (inner arm dyneins) produces sliding between the doublets, powers the axoneme, and causes ciliary beat. The form and frequency of beat are modulated in a highly complex manner by second messengers generated via ciliary membrane channels or coupled receptors and by actions of the radial spoke–central pair proteins. The radial spokes (Fig. 3.1) extend from each doublet microtubule to specific protein projections surrounding the central singlet microtubules (Smith and Yang, 2004). Orthologous proteins of different organisms form the identical structures and perform the same functions in corresponding axonemes. Moreover, mutations in these proteins lead to structural and motility defects in Chlamydomonas and, because of the corresponding defects in human cilia, to ciliopathies in man (Badano et al., 2006, Li et al., 2004, Satir and Christensen, 2008). As examples of human ciliopathies, defects in OADs lead to primary ciliary dyskinesia (PCD), defects in hydin lead to hydrocephalus and defects in IFT88 (polaris) lead to autosomal recessive polycystic kidney disease (PKD).

Specialized sensory cilia like the photoreceptor outer segment and primary cilia also possess an axoneme, a ciliary membrane, a ciliary necklace and they grow above a basal body by IFT. However, although axonemal structure is largely preserved, these cilia are often nonmotile because the dynein arms, the radial spokes, and proteins involved in dynein regulation are missing. In most cases, the central microtubules are also missing and the axonemes are referred to as 9 + 0. Examples abound in vertebrates, as such 9 + 0 “primary” cilia are found on most cell types. In contrast to motile function, the presence or absence of sensory function, regulated adhesion, and surface motility are less easily detected. These functions may be retained by most motile as well as nonmotile cilia.

Section snippets

The Link Between Ciliary Evolution and Eukaryotic Divergence

Conservation of primary sequence, protein composition, structure, and function throughout eukaryotic history as recorded in current phyletic divergence suggests a unitary origin of cilia at or very near the beginning of eukaryotic cell evolution. Certainly, the presence of cilia can be traced back to the last eukaryotic common ancestor (LECA) through analysis of gene/protein sequences and studies of ultrastructure in existing organisms. These determinations have been made possible only by the

Hypotheses of the Origin of Cilia

Three hypotheses of the origin and subsequent evolution of the cilium have been proposed. The first, the symbiotic model, derives cilia from a spirochete bacterium (Margulis, 1981). However, no comparative genomic evidence has been found to support a spirochete ancestry of the ciliary proteome. Given this and the cell biological difficulties with such a symbiotic cell fusion model we and others think that this explanation is highly unlikely.

The second hypothesis is autogenous origin of the

Statement of the hypothesis

The viral hypothesis (Fig. 3.2) suggests that the cilium evolves at a time after the invention of membrane trafficking in the protoeukaryotic cytoplasm. The sequence of events postulated is as follows.

An RNA enveloped virus with ninefold symmetry invades the cell. The basal structure of the virus is the cartwheel, each spoke of which initiates a triplet microtubule. The virus disassembles with the nucleic acid integrating into the evolving eukaryotic cell nucleus.

The virus reassembles in a

Autogenous origin of microtubule-organizing centers

An alternative to the viral origin of basal bodies and cilia is an autogenous model. In this model, the basal body structure evolved from pre-existing cellular components via the process of gene duplication and divergence and the final ninefold symmetry is the result of a coevolutionary process to optimize cilium-based motility. According to this model, basal body structure and axonemal structure tightly coevolved from the very beginning, and therefore neither structure was templated on the

Origin of Intraflagellar Transport and the Sensory Function of Cilia

The evolutionary history of centriolar and axonemal components suggests that protoeukaryotes must have already possessed a dynamic cytoskeleton when cilium evolution started (Cavalier-Smith, 2002). In addition, the history of IFT suggests that this protoeukaryotic cell also contained a secretory endomembrane system that was shaped by vesicle coat complexes and molecular motors (Jékely and Arendt, 2006) (Fig. 3.3). Based on these we can infer that the protoeukaryotic cell that started to evolve

The Evolution of Ciliary Motility

Regardless of whether centrioles and basal bodies evolved from a virus or via an autogenous mechanism, it is widely accepted that the ciliary axoneme evolved gradually and that ciliary motility was one of the driving forces. Motility provides an important selection mechanism, since a motile single-celled organism is far better able to find nutrients and to avoid predators and unfavorable conditions. Since primitive eukaryotes likely had actin and myosin and a well-developed amoeboid motility,

Acknowledgments

We thank Michael Cammer and Ann Holland for help in preparing this manuscript.

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