Genomic adaptation underlies nutrient-driven reprogramming in the malaria-causing parasite

Abstract

Parasites often depend on metabolic adaptation to the host environment. An adaptive feature of malaria-causing parasites is digestion of hemoglobin (HB) to acquire amino acids (AAs). Here we describe a link between nutrient availability and translation elongation-dependent regulation of gene expression as an adaptive strategy. We show that, unexpectedly, tRNA expression in P. falciparum does not match the decoding need as tRNAs decoding AAs that are rare in HB are lowly expressed. This discrepancy renders codons of HB-rare AAs inefficiently decoded and transcripts levels negatively correlated with the requirement of HB-rare AAs for protein synthesis, which are consistent with poor codon optimality causing co-translational mRNA decay. Intriguingly, proliferation-related genes have evolved to require a high level of HB-rare AAs in their encoded proteins, thereby allowing the parasite to control its proliferation by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elongation by maintaining a discordant tRNA profile as a mechanism to exploit variations in AA-composition among genes as an adaptation strategy.