Abstract

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities.

Highlights

  • Apoptosis-like programmed cell death (PCD) has been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium [1,2], Trypanosoma [3,4] and Leishmania [5]

  • We detected homologues of the apoptosis factors: DNases ZEN1, NUC1 and TSN when using BLASTP homology searches in the uniprot database. These analyses suggest that mitochondrial apoptosis factors are absent in T. vaginalis but that their function has been replaced by nuclear apoptosis factors

  • Apoptosis like PCD is induced by caspase-family proteases and the execution of apoptosis requires the release of endonuclease G (EndoG) and apoptosis induction factor (AIF) from the mitochondria

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Summary

Introduction

Apoptosis-like programmed cell death (PCD) has been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium [1,2], Trypanosoma [3,4] and Leishmania [5]. If different circumstances elicit an apoptosis response in different parasite species, a variety of regulatory mechanisms might be required, but could signal to the same execution machinery Another key gap in understanding apoptosis is how cells decide whether or not to initiate programmed death. Our BLASTP searches did not identify homologous proteins of these receptors in Plasmodium or Tetrahymena, supporting the suggestion that there is considerable variation in mechanisms regulating apoptosis-like PCD within protozoan parasites. These analyses suggest that mitochondrial apoptosis factors are absent in T. vaginalis but that their function has been replaced by nuclear apoptosis factors

Conclusions
20. Wyllie AH
Findings
40. Nedelcu AM
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