Abstract
Hypermutable simple sequence repeats (SSRs) are drivers of phase variation (PV) whose stochastic, high-frequency, reversible switches in gene expression are a common feature of several pathogenic bacterial species, including the human pathogen Campylobacter jejuni. Here we examine the distribution and conservation of known and putative SSR-driven phase variable genes – the phasome – in the genus Campylobacter. PhasomeIt, a new program, was specifically designed for rapid identification of SSR-mediated PV. This program detects the location, type and repeat number of every SSR. Each SSR is linked to a specific gene and its putative expression state. Other outputs include conservation of SSR-driven phase-variable genes and the ‘core phasome’ – the minimal set of PV genes in a phylogenetic grouping. Analysis of 77 complete Campylobacter genome sequences detected a ‘core phasome’ of conserved PV genes in each species and a large number of rare PV genes with few, or no, homologues in other genome sequences. Analysis of a set of partial genome sequences, with food-chain-associated metadata, detected evidence of a weak link between phasome and source host for disease-causing isolates of sequence type (ST)-828 but not the ST-21 or ST-45 complexes. Investigation of the phasomes in the genus Campylobacter provided evidence of overlapping but distinctive mechanisms of PV-mediated adaptation to specific niches. This suggests that the phasome could be involved in host adaptation and spread of campylobacters. Finally, this tool is malleable and will have utility for studying the distribution and genic effects of other repetitive elements in diverse bacterial species.
Highlights
Tandem DNA repeats of the same sequence, termed simple sequence repeats (SSRs) or microsatellites, are subject to high rates of changes in repeat number during DNA replication
The basic premise underpinning development of PhasomeIt was that putatively phase-variable genes can be identified in bacteria by analysis of SSRs in genome sequence data
PhasomeIt intergrates an SSR repeat finder (Bossref) with sequence analysis and homology searches to determine whether an SSR has the potential to drive phase variation (PV) and to determine the putative function(s) of the associated ORF (Fig. 1)
Summary
Tandem DNA repeats of the same sequence, termed simple sequence repeats (SSRs) or microsatellites, are subject to high rates of changes in repeat number during DNA replication. Transcriptional PV occurs when changes in repeat number of an intergenic SSR alters the activity of a promoter or other regulatory element. Both types of SSR-mediated PV are present in several bacterial species but with significant differences in the SSR types and in the phasome (defined as the numbers and types of phase-variable genes in a genome sequence) [3,4,5,6] Other types of repetitive tracts, such as the imperfect.
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