Comparative genomics of two protozoans Dictyostelium discoideum and Plasmodium falciparum reveals conserved as well as distinct regulatory pathways crucial for exploring novel therapeutic targets for Malaria.

Plasmodium falciparum, which causes life-threatening cerebral malaria has rapidly gained resistance against most frontline anti-malarial drugs, thereby generating an urgent need to develop novel therapeutic approaches. Conducting in-depth investigations on Plasmodium in its native form is challenging, thereby necessitating the requirement of an efficient model system. In line, mounting evidence suggests that Dictyostelium discoideum retains both conformational and functional properties of Plasmodium proteins, however, the true potential of Dictyostelium as a host system is not fully explored. In the present study, we have exploited comparative genomics as a tool to extract, compare, and curate the extensive data available on the organism-specific databases to evaluate if D. discoideum can be established as a prime model system for functional characterization of P. falciparum genes. Through comprehensive in silico analysis, we report that despite the presence of adaptation-specific genes, the two display noteworthy conservation in the housekeeping genes, signaling pathway components, transcription regulators, and post-translational modulators. Furthermore, through orthologue analysis, the known, potential, and novel drug target genes of P. falciparum were found to be significantly conserved in D. discoideum. Our findings advocate that D. discoideum can be employed to express and functionally characterize difficult-to-express P. falciparum genes.