Generalist malaria parasites and host imprinting: Unveiling transcriptional memory

Generalist parasites must rapidly adapt to diverse host environments to ensure their survival and transmission. Parasites may employ fixed genetic responses, transcriptional plasticity, or epigenetic mechanisms to optimize survival. The avian malaria parasite Plasmodium homocircumflexum serves as an ideal model for studying transcriptional variation and adaptive strategies. We experimentally inoculated P. homocircumflexum into different bird hosts, bypassing vector recombination, to investigate whether parasite gene expression remains stable across hosts, resets in response to new environments, or reflects epigenetic inheritance. Our study evaluates four potential mechanisms: (1) A universal gene expression profile (“one key fits all”), where expression remains stable across hosts. Our outcomes revealed that gene expression differed significantly depending on the host species and time post-infection, thus rejecting this hypothesis. (2) Complete transcriptional plasticity, where gene expression is fully determined by the recipient host. Contrary to this hypothesis, we observed that gene expression was primarily influenced by the donor at 8 days post-infection (dpi), whereas gene expression was more aligned with the recipient host at 16 dpi. (3) Epigenetic inheritance, where early-stage gene expression reflects the donor host but gradually adjusts to the recipient. Our results support this mechanism, as 2,647 differentially expressed genes (DEGs) were associated with donors at 8 dpi, whereas 271 DEGs were linked to the recipient by 16 dpi. (4) Selection-driven differentiation favoring specific haplotypes. This latter hypothesis was not supported since SNP analyses showed low genetic differentiation. These findings suggest a P. homocircumflexum transition from donor-dependent to recipient-dependent gene expression, likely mediated by epigenetic regulation and transcriptional plasticity.