Evolving Differentiation in African Trypanosomes

As multiple examples indicate that differentiation can be triggered by stress in protozoan parasites, we propose that stress response pathways are likely well suited to providing the frameworks for differentiation.

Selecting differentiation in trypanosomes as an exemplar, we discuss the parallels between the canonical differentiation pathway and recent observations of stresses from drug treatment and gene expression changes that indicate similar changes to protein expression as differentiation.

We propose a model whereby stress responses provide an original mechanism for survival in a novel environment and which, over time, become integrated with signalling pathways to increase differentiation efficiency and, hence, fitness.
Differentiation is a central aspect of the parasite life cycle and encompasses adaptation to both host and environment. If we accept that evolution cannot anticipate an organism’s needs as it enters a new environment, how do parasite differentiation pathways arise? The transition between vertebrate and insect stage African trypanosomes is probably one of the better studied and involves a cell-cycle arrested or ‘stumpy’ form that activates metabolic pathways advantageous to the parasite in the insect host. However, a range of stimuli and stress conditions can trigger similar changes, leading to formation of stumpy-like cellular states. We propose that the origin and optimisation of this differentiation program represents repurposing of a generic stress response to gain considerable gain-of-fitness associated with parasite transmission.