Phylogenetic evidence for frequent positive selection and recombination in the meningococcal surface antigen PorB

被引:78
作者
Urwin, R
Holmes, EC
Fox, AJ
Derrick, JP
Maiden, MCJ
机构
[1] Univ Oxford, Dept Zool, Oxford OX1 3PS, England
[2] Withington Hosp, Publ Hlth Lab, Meningococcus Ref Unit, Manchester M20 8LR, Lancs, England
[3] UMIST, Dept Biomol Sci, Manchester M60 1QD, Lancs, England
关键词
Neisseria meningitidis; porB; evolution; recombination; selection;
D O I
10.1093/oxfordjournals.molbev.a003991
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous estimates of rates of synonymous (d(S)) and nonsynonymous (d(N)) substitution among Neisseria meningitidis gene sequences suggested that the surface loops of the variable outer membrane protein PorB were under only weak selection pressure from the host immune response. These findings were consistent with studies indicating that PorB variants were not always protective in immunological and microbiological assays and questioned the suitability of this protein as a vaccine component. PorB, which is expressed at high levels on the surface of the meningococcus, has been implicated in mechanisms of pathogenesis and has also been used as a typing target in epidemiological investigations. In this work, using more precise estimates of selection pressures and recombination rates, we have shown that some residues in the surface loops of PorB are under very strong positive selection, as great as that observed in human immunodeficiency virus-1 surface glycoproteins, whereas amino acids within the loops and the membrane-spanning regions of the protein are under purifying selection, presumably because of structural constraints. Congruence tests showed that recombination occurred at a rate that was not sufficient to erase all phylogenetic similarity and did not greatly bias selection analysis. Homology models of PorB structure indicated that many strongly selected sites encoded residues that were predicted to be exposed to host immune responses, implying that this protein is under strong immune selection and requires further examination as a potential vaccine candidate. These data show that phylogenetic inference can be used to complement immunological and biochemical data in the choice of vaccine candidates.
引用
收藏
页码:1686 / 1694
页数:9
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