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Comparative Study
. 2017 Sep 5;12(9):e0184314.
doi: 10.1371/journal.pone.0184314. eCollection 2017.

Comparative Genomics and Phylogenomic Analyses of Lysine Riboswitch Distributions in Bacteria

Affiliations
Free PMC article
Comparative Study

Comparative Genomics and Phylogenomic Analyses of Lysine Riboswitch Distributions in Bacteria

Sumit Mukherjee et al. PLoS One. .
Free PMC article

Abstract

Riboswitches are cis-regulatory elements that regulate the expression of genes involved in biosynthesis or transport of a ligand that binds to them. Among the nearly 40 classes of riboswitches discovered so far, three are known to regulate the concentration of biologically encoded amino acids glycine, lysine, and glutamine. While some comparative genomics studies of riboswitches focusing on their gross distribution across different bacterial taxa have been carried out recently, systematic functional annotation and analysis of lysine riboswitches and the genes they regulate are still lacking. We analyzed 2785 complete bacterial genome sequences to systematically identify 468 lysine riboswitches (not counting hits from multiple strains of the same species) and obtain a detailed phylogenomic map of gene-specific lysine riboswitch distribution across diverse prokaryotic phyla. We find that lysine riboswitches are most abundant in Firmicutes and Gammaproteobacteria where they are found upstream to both biosynthesis and/or transporter genes. They are relatively rare in all other prokaryotic phyla where if present they are primarily found upstream to operons containing many lysine biosynthesis genes. The genome-wide study of the genetic organisation of the lysine riboswitches show considerable variation both within and across different Firmicute orders. Correlating the location of a riboswitch with its genomic context and its phylogenetic relationship with other evolutionarily related riboswitch carrying species, enables identification and annotation of many lysine biosynthesis, transporter and catabolic genes. It also reveals previously unknown patterns of lysine riboswitch distribution and gene/operon regulation and allows us to draw inferences about the possible point of origin of lysine riboswitches. Additionally, evidence of horizontal transfer of riboswitches was found between Firmicutes and Actinobacteria. Our analysis provides a useful resource that will lead to a better understanding of the evolution of these regulatory elements and prove to be beneficial for exploiting riboswitches for developing targeted therapies.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Lysine biosynthesis DAP pathway.
Lysine biosynthesis genes regulated by lysine riboswitches are shown in blue. Lysine biosynthesis genes which are not regulated by lysine riboswitches in any organisms are shown in red. Lysine biosynthesis genes found to be regulated by riboswitches in very few instances are highlighted in purple.
Fig 2
Fig 2. Phylogenomic distribution of riboswitch regulated lysine biosynthesis genes/operons and lysine transporter genes in the phylum Firmicutes.
The different biosynthesis and transporter genes are color-coded according to a scheme specified in the figure legend. Filled circles indicate both the riboswitch and the gene are present, unfilled circles indicate that the riboswitch is absent but the corresponding gene is present. Species highlighted in bold, maroon color possess riboswitches upstream to operons containing multiple biosynthesis genes all of which are represented by color-coded filled circles. Filled squares indicate both the riboswitch and the gene are present, unfilled squares indicate that the riboswitch is absent but the corresponding transporter gene is present.
Fig 3
Fig 3. Genome rearrangement and operon organizations in (A) Bacillales (B) Clostridiales and (C) Lactobacillales.
Blue and green filled rectangles represent lysine biosynthesis genes and those genes that are not involved in lysine biosynthesis, respectively. Red cross marks locations where an operon has split or a gene has been removed from an operon. A red plus sign marks location where one or more genes have been inserted into the operon. For cases where only the genus name is provided, all the species of that genus have the same operon structure.
Fig 4
Fig 4. Phylogenomic distribution of riboswitch regulated genes and operons involved in lysine biosynthesis and transport in the phylum Gammaproteobacteria.
Filled shapes (circle for biosynthesis and square for transporter genes) indicate both the riboswitch and the gene are present, unfilled shapes indicate that the riboswitch is absent but the corresponding gene is present. Species highlighted in bold maroon color possess a riboswitch upstream to an operon containing multiple biosynthesis genes all of which are represented by color-coded filled circles. The color-coding scheme is specified in the figure legend.
Fig 5
Fig 5. Phylogenomic distribution of riboswitch regulated genes and operons involved in lysine biosynthesis and transport in all other phylum excluding Firmicutes and Gammaproteobacteria.
Filled shapes (circle for biosynthesis, square for transporters genes and star for lysine catabolic genes) indicate both the riboswitch and the gene are present; unfilled shapes indicate that the riboswitch is absent but the corresponding gene is present. Species highlighted in bold maroon color possess a riboswitch upstream to an operon containing multiple biosynthesis genes all of which are represented by filled circles.
Fig 6
Fig 6. Phylogenetic tree of lysP/gabP transporter genes found in Firmicutes and Actinobacteria.
Potential HRT event has occurred between species highlighted in maroon color.
Fig 7
Fig 7. Phylogenetic tree of lysX-lysY genes found in Firmicutes and Actinobacteria.
Dotted lines represent the clade where a riboswitch is not present upstream to the lysX-lysY gene. Potential HRT event has occurred between species highlighted in maroon color.
Fig 8
Fig 8. Phylogenetic tree of lysine riboswitch regulated lysW genes of gammaproteobacteria.
The clade highlighted in the tree by maroon branches depicts the HRT event.

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Grant support

This work has been supported by University Grants Commission (UGC grant No. 6-7/2014(IC)) and Israel Science Foundation (ISF grant No. 9/14) grants awarded jointly to SS and DB under the India-Israel Joint Research Project 2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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