In Silico Ionomics Segregates Parasitic from Free-Living Eukaryotes

Abstract

Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

NephromycesEncodes a Urate Metabolism Pathway and Predicted Peroxisomes, Demonstrating That These Are Not Ancient Losses of Apicomplexans

“…A shift in lifestyle from obligate parasite to mutualistic symbiont is quite rare, and completely unknown from deep within a eukaryotic lineage with such a long evolutionary history of parasitism. One common consequence of a parasitic lifestyle is a loss of genes essential to free-living organisms (Greganova et al. 2013; Janouškovec et al.…”

Protean permeases: Diverse roles for membrane transport proteins in kinetoplastid protozoa

“…They also underscore the requirement for multiple transporters to shuttle the critical Fe 2+ cofactor into and within parasites. Of interest, in silico studies on ion transporters and channels in the genomes of 37 unicellular eukaryotes found that clustering of predicted transporters for iron and other transition metals were especially useful in distinguishing extracellular from obligate intracellular protists [32]. These comparative omics studies suggest that acquisition of iron is a selective force in the evolution of unicellular parasites and highlight the importance of this metal in the infectious life style.…”

TbIRK is a signature sequence free potassium channel from Trypanosoma brucei locating to acidocalcisomes

“…Evaluation of new potential drug targets in the parasites may be the first step towards this goal. In this perspective ion channels are promising subjects based on their pharmacological accessability, sequence divergence from their human counterparts 3 and lack of redundancy 4 .…”