Low complexity regions (LCRs) are a common feature shared by many genomes, but their evolutionary and functional significance remains mostly unknown. At the core of the uncertainty is a poor understanding of the mechanisms that regulate their retention in genomes, whether driven by natural selection or neutral evolution. Applying a comparative approach of LCRs to multiple strains and species is a powerful approach to identify patterns of conservation in these regions. Using this method, we investigate the evolutionary history of LCRs in the genus Plasmodium based on orthologous protein coding genes shared by 11 species and strains from primate and rodent-infecting pathogens. We find multiple lines of evidence in support of natural selection as a major evolutionary force shaping the composition and conservation of LCRs through time and signatures that their evolutionary paths are species specific. Our findings add a comparative analysis perspective to the debate on the evolution of LCRs and harness the power of sequence comparisons to identify potential functionally important LCR candidates.
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