From genome structure to function: insights into structural variation in microbiology

Abstract

Structural variation in bacterial genomes is an important evolutionary driver. Genomic rearrangements, such as inversions, duplications, and insertions, can regulate gene expression and promote niche adaptation. Importantly, many of these variations are reversible and preprogrammed to generate heterogeneity. While many tools have been developed to detect structural variation in eukaryotic genomes, variation in bacterial genomes and metagenomes remains understudied. However, recent advances in genome sequencing technology and the development of new bioinformatic pipelines hold promise in further understanding microbial genomics.

Figure 1:. SV reversibly alters restriction modification and methylation enzymes.

Restriction modification systems can both methylate and cleave DNA. DNA cleavage is one of the main mechanisms of bacteriophage defense. Whereas DNA methylation patterns are important both for self DNA recognition and transcriptional regulation. The restriction modification loci contains hsdR (restriction), hsdM (modification), and hsdS (specificity) genes. The hsdS gene contains two target recognition domains (TRD) which determine the specificity of the enzymes. The hsdS gene can be reversibly modified affecting its specificity. (A) In regions that vary by site specific recombination, loci contain multiple copies of hsdS. Generally, only one copy of hsdS (hsdS_A) is transcribed [13]. The additional copies of hsdS (hsdS_B, hsdS_C) function as alternative alleles. Site specific recombinases flip DNA sequences in between inverted repeats (dashed lines) and shuffle TRDs between the transcribed and non-transcribed hsdS genes [66]. Invertible systems have been observed in many bacteria including Streptococcus pneumoniae [12] and Bacteroides fragilis [67]. (B) In other organisms, hsdS gene specificity varies by slipped-strand mispairing. In many hsdS genes, simple nucleotide repeats separate TRDs [32]. Increases or decreases in the number or repeats can cause premature truncation. Truncated HsdS form dimers altering specificity. A well characterized example of slipped-strand mispairing is found in Neisseria gonorrhoeae [68].