Abstract

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.

Highlights

  • Low complexity regions (LCRs) are a common feature shared by many genomes, but their evolutionary and functional significance remains mostly unknown

  • We investigated LCRs in protein-coding regions of Plasmodia for four primary reasons: first, the use of protein-coding LCRs allows an evolutionary study of LCRs present in orthologous genes; second, the high frequency of LCRs in Plasmodium falciparum provides a large comparative baseline to determine the evolution of these regions in other Plasmodia species; third, the range of compositional biases in different Plasmodia is a useful property to test the effect of genome compositional biases on LCRs evolution; fourth, the availability of fully sequenced genomes of multiple species and strains of Plasmodia provides the necessary information for a long-term evolutionary study

  • We analyzed the compositional preference of three rodent-infecting plasmodia (P. berghei, P. yoelii, and P. chabaudi) that are AT-rich like Pf

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Summary

Introduction

Low complexity regions (LCRs) are a common feature shared by many genomes, but their evolutionary and functional significance remains mostly unknown. 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. Pvb, Pvm), P. cynomolgi (Pcy), and P. knowlesi (Pk) (collectively called the CVK group) and Plasmodium falciparum (Pf), which is the most studied genome within the Plasmodium genus These comparisons allow the exploration of evolutionary changes over ~50 million years of evolution and among species with different genome biases and host preferences[21,25,26,27]. Because the hosts of Pcy and Pk are primarily macaques, comparative genomics of these species with preferentially human-host plasmodia can provide insights into potentially host-specific evolutionary strategies and recent or ongoing adaptive changes

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