Generalist Malaria Parasites and Host Imprinting: Unveiling Transcriptional Memory

Abstract

Plasmodium homocircumflexum; Adaptive strategies; Avian malaria

Plasmodium homocircumflexum; Estrategias adaptativas; Malaria aviar

Plasmodium homocircumflexum; Estratègies adaptatives; Malària aviar

Generalist parasites must adapt to diverse host environments to ensure their survival and transmission. These adaptations can involve fixed genetic responses, transcriptional plasticity, or epigenetic mechanisms. The avian malaria parasite Plasmodium homocircumflexum offers an ideal model for studying transcriptional variation across hosts. We experimentally inoculated P. homocircumflexum into different bird species, bypassing the vector, to assess whether gene expression remains stable across hosts, resets in response to new environments, or reflects epigenetic inheritance. We tested two alternative hypotheses: (i) universal gene expression profile (“one key fits all”), where parasite expression remains consistent across hosts. Our outcomes revealed that gene expression differed significantly depending on the host species and time postinfection, rejecting this hypothesis. (ii) Transcriptional plasticity, where gene expression is determined by the recipient host. Contrary to this hypothesis, we observed that gene expression was primarily influenced by the donor at 8 d postinfection (dpi), whereas gene expression was more aligned with the recipient host at 16 dpi. We also explored two mechanisms to explain these patterns: (i) epigenetic inheritance, whereby early transcription reflects the donor environment but adjusts over time, and (ii) genetic differentiation selecting for specific haplotypes. Our data support mechanism (i): 2,647 differentially expressed genes (DEGs) were associated with the donor at 8 dpi, while only 271 DEGs were linked to the recipient at 16 dpi. Single Nucleotide Polymorphism analyses revealed low genetic differentiation, rejecting mechanism (ii). These findings suggest that P. homocircumflexum undergoes a shift from donor-dependent to recipient-dependent gene expression, likely driven by epigenetic regulation and transcriptional plasticity.

Funding was provided by the Junta de Extremadura (PO17024, postdoc grant) to L.G.-L., the Spanish Ministry of Science and Innovation (PID2022-140397NB-I00) to A.M., and LA4 (R + D + I program in the Biodiversity Area financed with the funds of the FEDER Extremadura 2021–2027 Operational Program of the Recovery, Transformation and Resilience Plan) to L.G.-L., and A.M. V.P. obtained funding from the Research Council of Lithuania (LMTLT) (project no. S-MIP-22-52). O.H. obtained funding from the Swedish Research Council (VR 2016-03419 and 2021-03663). All the authors would like to thank Ananias Escalante for taking the time to read the manuscript and for his inspiring ideas.