Mechanisms of adaptation and evolution in Toxoplasma gondii

Toxoplasma has high host flexibility, infecting all nucleated cells of mammals and birds. This implies that during its infective process the parasite must constantly adapt to different environmental situations, which in turn leads to modifications in its metabolism, regulation of gene transcription, translation of mRNAs and stage specific factors. There are conserved pathways that support these adaptations, which we aim to elucidate in this review. We begin by exploring the widespread epigenetic mechanisms and transcription regulators, continue with the supportive role of Heat Shock Proteins (Hsp), the translation regulation, stress granules, and finish with the emergence of contingency genes in highly variable genomic domains, such as subtelomeres. Within epigenetics, the discovery of a new histone variant of the H2B family (H2B.Z), contributing to T. gondii virulence and differentiation, but also gene expression regulation and its association with the metabolic state of the parasite, is highlighted. Associated with the regulation of gene expression are transcription factors (TFs). An overview of the main findings on TF and development is presented. We also emphasize the role of Hsp90 and Tgj1 in T. gondii metabolic fitness and the regulation of protein translation. Translation regulation is also highlighted as a mechanism for adaptation to conditions encountered by the parasite as well as stress granules containing mRNA and proteins generated in the extracellular tachyzoite. Another important aspect in evolution and adaptability are the subtelomeres because of their high variability and gene duplication rate. Toxoplasma possess multigene families of membrane proteins and contingency genes that are associated with different metabolic stresses. Among them parasite differentiation and environmental stresses stand out, including those that lead tachyzoite to bradyzoite conversion. Finally, we are interested in positioning protozoa as valuable evolution models, focusing on research related to the Extended Evolutionary Synthesis, based on models recently generated, such as extracellular adaptation and ex vivo cyst recrudescence.