Cell suicide in multi-cellular creatures

Cell suicide programs play essential and well-documented roles in the development and maintenance of multi-cellular organisms. The evolution of cell death in multicellular organisms is readily explained because an individual's cells are clonally related and so have a shared goal in the successful development and maintenance of their ‘body'. For this reason, cell death by genetically controlled and tightly regulated processes was assumed only to have evolved in multicellular taxa.

Apoptosis in cells of multicellular animals is ‘diagnosed' when some or all of the following markers are observed: DNA fragmentation, chromatin condensation, membrane blebbing, formation of apoptotic bodies, cell shrinking, movement of phosphatidylserine to the outside of the plasma membrane, cleavage of proteins by caspases, and release of proteins from mitochondria. Necrotic death does not normally involve these markers because the severe damage involved results in rapid membrane permeability and leakage of cell contents.

Cell suicide in malaria parasites

Multiple markers of apoptosis have been observed in both mosquito and blood stages of malaria parasites. The most comprehensive studies have focussed on the rodent malaria parasite P. berghei, due to the ease of in vitro and in vivo manipulation of this model. When a mosquito vector takes a blood meal from an infected host, male and female parasite stages (gametocytes) rapidly differentiate into gametes and mate in the midgut. Fertilised females then develop into motile ookinete stages, which penetrate the midgut wall of their vector, encyst, and produce parasite stages that are infective to new hosts. In P. berghei, a number of ookinetes undergo apoptosis like cell death instead of attempting to invade the midgut wall of their vector. Markers of apoptosis observed in ookinetes include chromatin condensation, DNA fragmentation, and the activity of caspase-like proteases. This phenomenon occurs independently of mosquito and host blood factors and is not unique to Plasmodium parasites; evidence of apoptosis across a range of protozoan parasites (including Leishmania, Trypanosoma and Toxoplasma) is rapidly accumulating.

Discovering cell death in malaria and other unicellular parasites has resulted in controversy over fundamental questions about the evolution of programmed cell-death:  According to"Darwinian Survival of the Fittest" parasites are expected to evolve strategies to maximise their proliferation not their death.

To date, most research effort has focussed on unravelling the genetic mechanisms and physiological pathways involved in apoptosis so evolutionary explanations for why unicellular parasites undergo apoptosis remain untested. It is possible that parasites use apoptosis to "altruistically" self-regulate their number to avoid excessive infection levels that could kill their vectors before transmission to new hosts has occurred. This explanation assumes that vector survival is negatively related to parasite burden and apoptosis is a co-operative (altruistic) trait because parasites are using apoptosis to benefit the surviving parasites.

Regulating parasite numbers to prolong vector survival would benefit survivors, as would reducing competition for resources between parasites. The question of whether malaria infection is harmful to mosquitoes is not yet resolved and this may be due to varying levels of parasite apoptosis. If apoptosis is a cooperative trait it will be more frequent in infections in which parasites are genetically related because parasites should only undergo apoptosis when their actions will benefit their kin. Alternatively, in genetically diverse infections, competition for resources is likely to occur and parasites would benefit from inducing their unrelated competitors to undergo apoptosis. Investigating the relationship between apoptosis and the genetic diversity of infections is key to understanding the evolution and maintenance of this trait.