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Long-term evolution of antigen repertoires among carried meningococci.

Buckee CO, Gupta S, Kriz P, Maiden MC, Jolley KA - Proc. Biol. Sci. (2010)

Bottom Line: For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure.The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination.We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. caroline.buckee@zoo.ox.ac.uk

ABSTRACT
Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.

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The association between different pairs of loci over 26 years in the Czech Republic. D* values for each pair of loci was calculated. The boxplots show the median (red line), lower and upper quartiles (blue box) and the extent of the range (whiskers) for those loci that involved more than one comparison; for example, the calculation of D* for each housekeeping gene compared with every other housekeeping gene led to a total of 21 D* scores. For the PorA VR associations, only a single metric was computed between VR1 and VR2 (hence the single line shown on the plot). For the FetA∶PorA VR comparisons, two calculations were made: FetA versus PorA VR1 and FetA versus PorA VR2 (shown by the blue box). ‘VR’ refers to the variable regions of PorA, ‘hk’ refers to housekeeping genes, and ‘FetA’ represents the variable region of FetA. The concatenation of these indicates the comparison made. The PorA VR and housekeeping gene associations were significantly higher than the other two-locus comparisons (F = 108.15, p = 10−11), and the PorA VR associations were significantly different from the housekeeping gene associations, but only marginally (F = 6.32, p = 0.0189).
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RSPB20092033F1: The association between different pairs of loci over 26 years in the Czech Republic. D* values for each pair of loci was calculated. The boxplots show the median (red line), lower and upper quartiles (blue box) and the extent of the range (whiskers) for those loci that involved more than one comparison; for example, the calculation of D* for each housekeeping gene compared with every other housekeeping gene led to a total of 21 D* scores. For the PorA VR associations, only a single metric was computed between VR1 and VR2 (hence the single line shown on the plot). For the FetA∶PorA VR comparisons, two calculations were made: FetA versus PorA VR1 and FetA versus PorA VR2 (shown by the blue box). ‘VR’ refers to the variable regions of PorA, ‘hk’ refers to housekeeping genes, and ‘FetA’ represents the variable region of FetA. The concatenation of these indicates the comparison made. The PorA VR and housekeeping gene associations were significantly higher than the other two-locus comparisons (F = 108.15, p = 10−11), and the PorA VR associations were significantly different from the housekeeping gene associations, but only marginally (F = 6.32, p = 0.0189).

Mentions: The linkage statistic D* (Hedrick & Thomson 1986) was used to test the stability of associations between different loci over the 27 years. PorA variable regions showed relatively high D* values, indicative of strong, stable associations between the two regions over time. However, both VR1∶FetA and VR2∶FetA comparisons had a low D* value in comparison to the PorA variable regions, indicating that linkage between these loci was not maintained to the same extent (figure 1). Combinations of VR2∶FetA changed over the period of the study, with particular combinations changing in dominance. For example, 2-2∶F4-3, representative of the ST-549 complex, was seen extensively in 1972–1973 (42 isolates, 18%), but then was not observed again, whereas 3 : F3-6 was predominant in 1974–1975 (24 isolates, 11%). The emergence of the ST-11 complex in 1993–1994 was marked by the 2∶F3-6 combination (35 isolates, 12%), which was not observed previously. The housekeeping gene versus housekeeping gene linkage was high over time (figure 1), significantly higher than the association between housekeeping and antigenic genes. The lower linkage of the PorA VRs and FetA with the housekeeping genes suggests that stable lineages defined by housekeeping genes have a fluctuating association with particular antigenic determinants, as is also evident from a qualitative inspection of the data and previous analyses (Buckee et al. 2008). Note that we use D* here as a relative rather than absolute measure of association between two loci.


Long-term evolution of antigen repertoires among carried meningococci.

Buckee CO, Gupta S, Kriz P, Maiden MC, Jolley KA - Proc. Biol. Sci. (2010)

The association between different pairs of loci over 26 years in the Czech Republic. D* values for each pair of loci was calculated. The boxplots show the median (red line), lower and upper quartiles (blue box) and the extent of the range (whiskers) for those loci that involved more than one comparison; for example, the calculation of D* for each housekeeping gene compared with every other housekeeping gene led to a total of 21 D* scores. For the PorA VR associations, only a single metric was computed between VR1 and VR2 (hence the single line shown on the plot). For the FetA∶PorA VR comparisons, two calculations were made: FetA versus PorA VR1 and FetA versus PorA VR2 (shown by the blue box). ‘VR’ refers to the variable regions of PorA, ‘hk’ refers to housekeeping genes, and ‘FetA’ represents the variable region of FetA. The concatenation of these indicates the comparison made. The PorA VR and housekeeping gene associations were significantly higher than the other two-locus comparisons (F = 108.15, p = 10−11), and the PorA VR associations were significantly different from the housekeeping gene associations, but only marginally (F = 6.32, p = 0.0189).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2871849&req=5

RSPB20092033F1: The association between different pairs of loci over 26 years in the Czech Republic. D* values for each pair of loci was calculated. The boxplots show the median (red line), lower and upper quartiles (blue box) and the extent of the range (whiskers) for those loci that involved more than one comparison; for example, the calculation of D* for each housekeeping gene compared with every other housekeeping gene led to a total of 21 D* scores. For the PorA VR associations, only a single metric was computed between VR1 and VR2 (hence the single line shown on the plot). For the FetA∶PorA VR comparisons, two calculations were made: FetA versus PorA VR1 and FetA versus PorA VR2 (shown by the blue box). ‘VR’ refers to the variable regions of PorA, ‘hk’ refers to housekeeping genes, and ‘FetA’ represents the variable region of FetA. The concatenation of these indicates the comparison made. The PorA VR and housekeeping gene associations were significantly higher than the other two-locus comparisons (F = 108.15, p = 10−11), and the PorA VR associations were significantly different from the housekeeping gene associations, but only marginally (F = 6.32, p = 0.0189).
Mentions: The linkage statistic D* (Hedrick & Thomson 1986) was used to test the stability of associations between different loci over the 27 years. PorA variable regions showed relatively high D* values, indicative of strong, stable associations between the two regions over time. However, both VR1∶FetA and VR2∶FetA comparisons had a low D* value in comparison to the PorA variable regions, indicating that linkage between these loci was not maintained to the same extent (figure 1). Combinations of VR2∶FetA changed over the period of the study, with particular combinations changing in dominance. For example, 2-2∶F4-3, representative of the ST-549 complex, was seen extensively in 1972–1973 (42 isolates, 18%), but then was not observed again, whereas 3 : F3-6 was predominant in 1974–1975 (24 isolates, 11%). The emergence of the ST-11 complex in 1993–1994 was marked by the 2∶F3-6 combination (35 isolates, 12%), which was not observed previously. The housekeeping gene versus housekeeping gene linkage was high over time (figure 1), significantly higher than the association between housekeeping and antigenic genes. The lower linkage of the PorA VRs and FetA with the housekeeping genes suggests that stable lineages defined by housekeeping genes have a fluctuating association with particular antigenic determinants, as is also evident from a qualitative inspection of the data and previous analyses (Buckee et al. 2008). Note that we use D* here as a relative rather than absolute measure of association between two loci.

Bottom Line: For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure.The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination.We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. caroline.buckee@zoo.ox.ac.uk

ABSTRACT
Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.

Show MeSH