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

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.

In-Silico Analysis Highlights the Existence in Members of Burkholderia cepacia Complex of a New Class of Adhesins Possessing Collagen-like Domains

“…In terms of function, for bacteria, Peng et al [ 51 ] identified a correlation between intrinsically disordered regions and DNA and RNA binding, as well as sporulation, catabolic and metabolic processes, and pathogenesis. Mier et al [ 54 ] also suggest that LCR are more represented in the outer membrane and extracellular proteins in bacteria, being involved in host–pathogen interactions. These discoveries unravel the importance of disorder and LCR in proteins associated with pathogenicity and adhesion processes, encouraging further study of the importance of these domains in CLPs.…”

Identification of potential molecular mimicry in pathogen-host interactions

“…An LCR motif found across species may be crucial in host-pathogen interactions, or it may perform an endogenous function common in both organisms and not part of the interactions between pathogen and host. Given their functional importance alongside their role in hostpathogen interactions [52,53] and that mutation rates increase with proximity to LCRs [54][55][56][57][58], it is likely that host regulatory LCRs are mimicked by pathogens. However, it is incredibly challenging to identify the function of an LCR.…”

Improved Resolution of Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Using Oxford Nanopore R10 Sequencing Chemistry

“…Resolution of these low-complexity regions (LCRs) has been a challenge for many sequencing platforms, and has limited the adoption of nanopore sequencing for widespread HPAIV genomic surveillance 20 . Accurately sequencing LCRs is important for many pathogens relevant to human and animal health [30][31][32][33] .…”