Chapter 7 : Mechanisms of Genome Plasticity in : Fighting Change with Change

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This chapter on mechanisms of genome plasticity in initially gives a short overview over the genetic variability at the population level and some peculiarities of meningococcal genome organization as revealed by genome sequencing projects. Later, the focus is on genetic mechanisms and genomic features that are paramount for the generation of genomic flexibility, and a brief account of the genetic basis of virulence in as far as it is known today. Exogenous and endogenous stress induces DNA damage in the meningococcal genome that must be repaired, and DNA repair mechanisms are therefore likely to have a key role in meningococcal genome dynamics. So far, has served as the prime model organism for DNA repair systems in other microorganisms such as . The majority of strong mutators found in a number of bacterial species have a defective MMR pathway due to the inactivation of or genes. In addition to global mutation and phase variation, intragenomic as well as intergenomic recombination is of pivotal importance for the generation of genome flexibility in , and one of the most striking characteristics of the meningococcal genomes is the abundance and diversity of repetitive DNA serving as potential target sites for homologous recombination or replication slippage.

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
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Image of FIGURE 1

The genomes of . (A) Circular representation of the Z2471 genome. The concentric circles show, reading inwards, the scale in megabases, with the origin of replication indicated; predicted coding sequences clockwise (dark green) and counterclockwise (light green); neisserial uptake sequences (red); dRS3 sequences (dark orange); RS elements (light orange); dispersed repeats (Correia, ATR, REP2-5; black); IS elements and phage (narrow ticks and wide bars respectively; turquoise); and tandem repeats (dark blue). The inner histogram shows a plot of (G−C)/(G+C) with values greater than zero in yellow and less than zero in orange. The figure was taken from and is reprinted by permission from Macmillan Publishers Ltd.(, copyright 2000). (B) Annotated multiple whole-genome alignment. For each genome, the order of locally colinear blocks (LCBs) is given as a series of colored blocks with the putative origin of replication, designated , being indicated by a black rectangle. The genomic locations of dRS3 elements are depicted by short black vertical lines below the corresponding LCB order images. LCBs identically present in the four genomes are given in the same colors, and horizontally flipped LCBs identify chromosomal inversions with respect to the genome of a14 (e.g., the inversion designated Inv1 in the genome of Z2491 composed of two LCBs). Gaps or white spaces in the LCB order image indicate regions not (identically) present in all four genomes such as different prophages (Φ), genomic islands (GI), regions with deviating G+C content termed islands of horizontal transfer (IHT), or a region duplicated only in strain MC58 (D). In addition, the different chromosomal positions of are shown, as well as some putative composite transposons (T1 in FAM18 and T2 in MC58), the 20-kb region that is inverted in the three disease isolates (Inv2), and the position of the capsule gene locus (C). The figure was taken from . Copyright 2008 National Academy of Sciences, U.S.A.

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
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Image of FIGURE 2

Mechanisms of gene variation in (A) Phase variation at the capsule locus. In serogroup B meningococci starting from -acetylglucosamine-6-phosphate, the synthesis of the capsular polysaccharide, a homopolymer of α-2,8-linked -acetylneuraminic acid, involves four enzymatic steps. The encoding genes are organized into a polycistronic operon, and the last gene in this operon, , contains a stretch of seven consecutive cytidines in its 5′ coding region. The molecular mechanism that mediates phase variation at is RecA-independent slipped-strand mispairing of the polycytidine tract during DNA replication or repair. The resulting insertion or deletion of a single cytidine leads to a frameshift in the coding sequence and consequently to termination of translation at premature stop codons. As this process is reversible and occurs at a frequency of about 1 in 1,000 to 1 in 10,000 bacterial cells, this allows meningococci a rapid and reversible on/off switch of capsule synthesis ( ). In addition, capsule expression can be modulated based on the reversible inactivation of by insertion/excision of the insertion sequence element IS( ) (schematic depiction not drawn to scale). (B) Gene conversion at the /locus ( ). Meningococcal type IV pili consist of thousands of pilin (PilE) subunits polymerized into long fibers. The PilE protein contains a highly conserved N-terminal domain and a variable C-terminal domain, the latter determining the antigenicity of the pili. The variable region is the result of a nonreciprocal transfer of DNA from one of many silent partial loci to the single expression locus. The silent loci, which are sometimes present several hundred base pairs away from the expression locus, can donate a stretch of nucleotides, on the basis of short sequence homology. The genetic mechanism proceeds through a form of gene conversion that requires RecA and several crossover events during recombination (schematic depiction not drawn to scale). (C) Three-dimensional model of the PilE protein. The N and C termini are indicated, and the variable C terminus is highlighted in yellow. The structure was retrieved from the PDB database (2HI2) ( ) and visualized with the SwissPdb Viewer (http://www.expasy.org/spdbv/) ( ).

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
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Meningococcal genomes sequenced by September 2009

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
Generic image for table

Phase-and antigen-variable genes in

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07

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