Distinct repeat architecture landscapes in the proteomes of protozoan parasites

Protozoan parasites cause major infectious diseases and pose persistent global health challenges, particularly the emergence of drug-resistant strains. Tandem repeats and other repetitive architectures are widespread in proteomes and have been implicated in host-parasite interactions, immune evasion, and antigenicity. However, repeat-containing proteins (RPs) exhibit highly diverse architectures that extend beyond simple motif reiteration, making their comprehensive and quantitative characterization challenging. In this study, we performed bioinformatics analysis of repeat architectures in protozoan proteins. In addition to the established repeat-detection approaches, we developed a new algorithm, Drepper, which quantifies repeat-architecture complexity. By integrating diverse repeat-related features, we clustered RPs across species and identified distinct groups associated with parasite lineages. Notably, we identified a high-complexity, repeat-rich (HCRR) cluster enriched in Plasmodium proteins and a low-complexity, repeat-rich (LCRR) cluster enriched in Trypanosoma and Leishmania proteins. Functional, evolutionary, and structural analyses revealed that LCRR cluster is enriched in flagellar-related proteins, low-complexity repeat architectures may be maintained through concerted evolution, and, compared with HCRR, it shows a greater tendency to adopt defined three-dimensional structures. Taken together, our results reveal lineage-specific strategies in protozoan repeat architectures and provide a quantitative framework for studying their biological and evolutionary roles.