The Nature of Programmed Cell Death

Abstract

In multicellular organisms, cells are frequently programmed to die. This makes good sense: cells that fail to, or are no longer playing important roles are eliminated. From the cell’s perspective, this also makes sense, since somatic cells in multicellular organisms require the cooperation of clonal relatives. In unicellular organisms, however, programmed cell death (PCD) poses a difficult and unresolved evolutionary problem. The empirical evidence for PCD in diverse microbial taxa has spurred debates about what precisely PCD means in the case of unicellular organisms (how it should be defined). In this article, we survey the concepts of PCD in the literature and the selective pressures associated with its evolution. We show that definitions of PCD have been almost entirely mechanistic and fail to separate questions concerning what PCD fundamentally is from questions about the kinds of mechanisms that realize PCD. We conclude that an evolutionary definition is best able to distinguish PCD from closely related phenomena. Specifically, we define “true” PCD as an adaptation for death triggered by abiotic or biotic environmental stresses. True PCD is thus not only an evolutionary product but must also have been a target of selection. Apparent PCD resulting from pleiotropy, genetic drift, or trade-offs is not true PCD. We call this “ersatz PCD.”