Genetics of Apoptosis

8.

Evolution of cell death: caspase-mediated

mechanisms in early metazoans; noncaspase

mechanisms in single-celled eukaryotes

Angelika Böttger and Charles N.David

1.

Introduction

Apoptosis, or programmed cell death, has become a central topic in cell biologic
research, and its biochemical mechanisms have been studied extensively in a number
of model organisms including Caenorhabditis, Drosophila, and mouse, and in human
cell lines. In these animals and cell lines, the main cell-death pathway is dependent
on a family of cysteine proteases, the caspases (see Chapter 2). Recent work has now
identified caspases and programmed cell death in Cnidaria, the oldest metazoan
phylum, and thus pushed the origin of this process back to the threshold of
multicellular evolution (Cikala et al., 1999; Miller et al., 2000; Seipp et al., 2001).
Since caspases have not yet been identified in single-celled eukaryotes (Aravind et
al., 1999), it appears that the caspase-dependent cell-death pathway may have arisen
coincident with the evolution of metazoan animals. The process of programmed cell
death, by comparison, appears to have evolved much earlier and perhaps several times
independently, since a number of single-cell eukaryotes, including the slime mold
Dictyostelium, the ciliate Tetrahymena, and the protozoan Trypanosoma brucei, exhibit
cell-death programs but appear to lack caspases (Davis et al., 1992; Cornillon et al.,
1994; Ameisen et al., 1995). These cell-death programs are accompanied by some,
but not all, of the morphologic features characteristic of apoptosis. In the case of
Dictyostelium, cell death has been shown to be associated with release of apoptosis-
inducing factor (AIF) from mitochondria. This cell-death program appears to be an
alternative to the caspase-dependent pathway. Since it is also present in higher
metazoans (Susin et al., 1999), it may represent an ancient form of programmed cell
death which has been maintained in evolution.
The first part of this chapter will focus on apoptosis in cnidarians, specifically in
the fresh-water hydrozoan polyp Hydra and in the colonial marine hydrozoan
Hydractinia. We will begin with three examples of apoptosis in Hydra and Hydractinia
that have been well analyzed in the past three years. In the second part of this chapter,
we will consider examples of programmed cell death in three single-celled eukaryotes.