Abstract Motivation The Codon usage bias, the preference for certain “silent” codons over others, is determined by a competition between two main forces: mutational pressure (random changes in DNA) and translational selection (the need for efficient protein production). However, we still lack a clear understanding of how this balance operates differently within the mitochondrial versus the nuclear genomes. Results Here, we perform a comparative analysis of 120 parasitic helminths (Platyhelminthes and Nematoda), integrating mitochondrial genomes with matched nuclear transcriptomes to dissect the drivers of codon bias. Mitochondrial genes exhibit an AT-rich bias due to mutational factors, while nuclear codon preferences strongly correlate with gene expression, with highly-expressed genes utilizing optimal codons for efficiency. Across both compartments, patterns confirm pervasive selection acting on these seemingly “silent” sites, with codon optimization concentrated in the essential core oxidative phosphorylation (OXPHOS) subunits (like COX1, COX2) but relaxed in accessory genes. Crucially, comparative analyses revealed both mitonuclear coadaptation and, in some lineages, compartmental decoupling, demonstrating that parasites employ diverse evolutionary strategies to assemble their functional respiratory system, thus establishing that synonymous codons encode important functional adaptation relevant to parasite biology and control.
Das et al. (Fri,) studied this question.