The Conservation of Low Complexity Regions in Bacterial Proteins Depends on the Pathogenicity of the Strain and Subcellular Location of the Protein.

Pablo Mier,Miguel A Andrade-Navarro

doi:10.3390/genes12030451

Abstract

Low complexity regions (LCRs) in proteins are characterized by amino acid frequencies that differ from the average. These regions evolve faster and tend to be less conserved between homologs than globular domains. They are not common in bacteria, as compared to their prevalence in eukaryotes. Studying their conservation could help provide hypotheses about their function. To obtain the appropriate evolutionary focus for this rapidly evolving feature, here we study the conservation of LCRs in bacterial strains and compare their high variability to the closeness of the strains. For this, we selected 20 taxonomically diverse bacterial species and obtained the completely sequenced proteomes of two strains per species. We calculated all orthologous pairs for each of the 20 strain pairs. Per orthologous pair, we computed the conservation of two types of LCRs: compositionally biased regions (CBRs) and homorepeats (polyX). Our results show that, in bacteria, Q-rich CBRs are the most conserved, while A-rich CBRs and polyA are the most variable. LCRs have generally higher conservation when comparing pathogenic strains. However, this result depends on protein subcellular location: LCRs accumulate in extracellular and outer membrane proteins, with conservation increased in the extracellular proteins of pathogens, and decreased for polyX in the outer membrane proteins of pathogens. We conclude that these dependencies support the functional importance of LCRs in host–pathogen interactions.

Highlights

Low complexity regions (LCRs) are protein regions with a skewed amino acid composition [1]
In order to determine the extent to which LCRs are conserved in bacterial species, and perhaps functional, we decided to focus on pairs of bacterial strains
Results show the higher conservation of LCRs in pathogenic strain pairs (Figure 3d,e), contrasting the conservation of domains in non-pathogenic strain pairs (Figure 3f). These results suggest that LCR conservation is significantly stronger in pathogenic strains compared to non-pathogenic strains, and that this difference in conservation does not apply to domains

Summary

Introduction

Low complexity regions (LCRs) are protein regions with a skewed amino acid composition [1]. Both rely on a higher proportion of one amino acid, either scattered (CBRs) or localized (polyX) [1] They show a high mutation rate [2]; as a result, orthologous proteins can have very different LCRs. In addition to having high variability, LCRs have unusual structural properties, making their study more complex than that of globular domains. The abundance of completely sequenced prokaryotic genomes enables the analysis of the conservation of protein features across homologs, which can be employed to provide hypotheses about LCR conservation and function in prokaryotes. This approach was used to provide evidence that the conservation of LCRs can be connected to general functions in prokaryotes [7]: translation, nucleic acid binding, metal-ion binding, and protein folding

Methods

Results

Conclusion