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Measuring immune selection

Published online by Cambridge University Press:  29 May 2003

D. J. CONWAY  and
S. D. POLLEY
D. J. CONWAY
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT
S. D. POLLEY
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT
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Abstract

Immune responses that kill pathogens or reduce their reproductive rate are generally important in protecting hosts from infection and disease. Pathogens that escape the full impact of such responses will survive, and any heritable genetic basis of this evasion will be selected. Due to the memory component of vertebrate immune responses, pathogens with rare alleles of a target antigen can have an advantage over those with common alleles, leading to the maintenance of a polymorphism. At the genetic level, there ought to be detectable signatures of balancing selection in the genes encoding these antigens. Here, methods for identifying these selective signatures are reviewed. Their practical utility for identifying which antigens are targets of protective immune responses is discussed.

Keywords

Antigensgenesprotective immunitynatural selectiontests of neutrality
Type
Research Article
Information
Parasitology , Volume 125 , Issue 7 , May 2002 , pp. S3 - S16
Copyright
© 2002 Cambridge University Press

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References

ACHTMAN, M., ZURTH, K., MORELLI, G., TORREA, G., GUIYOULE, A. & CARNIEL, E. (1999). Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proceedings of The National Academy of Sciences, USA 96, 14043–14048.CrossRefGoogle Scholar
AIDOO, M., LALVANI, A., ALLSOPP, C. E. M., PLEBANSKI, M., MEISNER, S. J., KRAUSA, P., BROWNING, M., MORRISJONES, S., GOTCH, F., FIDOCK, D. A., TAKIGUCHI, M., ROBSON, K. J. H., GREENWOOD, B. M., DRUILHE, P., WHITTLE, H. C. & HILL, A. V. S. (1995). Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria. Lancet 345, 1003–1007.CrossRefGoogle Scholar
ALLEN, T. M., O'CONNOR, D. H., JING, P., DZURIS, J. L., MOTHE, B. R., VOGEL, T. U., DUNPHY, E. & LLEBL, M. E. ETAL. (2000). Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 407, 386–390.Google Scholar
ALLRED, D. R., CARLTON, J. M. R., SATCHER, R. L., LONG, J. A., BROWN, W. C., PATTERSON, P. E., O'CONNOR, R. M. & STROUP, S. E. (2000). The ves multigene family of B. bovis encodes components of rapid antigenic variation at the infected erythrocyte surface. Molecular Cell 5, 153–162.Google Scholar
ANDERSON, T. J. C. & DAY, K. P. (2000). Geographical structure and sequence evolution as inferred from the Plasmodium falciparum S-antigen locus. Molecular and Biochemical Parasitology 106, 321–326.CrossRefGoogle Scholar
BABIKER, H. A., SATTI, G. & WALLIKER, D. (1995). Genetic changes in the population of Plasmodium falciparum in a Sudanese village over a three year period. American Journal of Tropical Medicine and Hygiene 53, 7–15.CrossRefGoogle Scholar
BINKS, R. H., BAUM, J., ODUOLA, A. M. J., ARNOT, D. E., BABIKER, H. A., KREMSNER, P. G., ROPER, C., GREENWOOD, B. M. & CONWAY, D. J. (2001). Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (eba-175) gene. Molecular and Biochemical Parasitology 114, 63–70.CrossRefGoogle Scholar
BOJANG, K. A., MILLIGAN, P. J. M., PINDER, M., VIGNERON, L., ALLOUECHE, A., KESTER, K. E., BALLOU, W. R., CONWAY, D. J., REECE, W. H. H., GOTHARD, P., YAMUAH, L., DELCHAMBRE, M., VOSS, G., GREENWOOD, B. M., HILL, A., MCADAM, K. P. W. J., TORNIEPORTH, N., COHEN, J. D. & DOHERTY, T. (2001). Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358, 1927–1934.CrossRefGoogle Scholar
BORST, P. & ULBERT, S. (2001). Control of VSG expression sites. Molecular and Biochemical Parasitology 114, 17–27.CrossRefGoogle Scholar
BRAYTON, K. A., KNOWLES, D. P., MCGUIRE, T. C. & PALMER, G. H. (2001). Efficient use of a small genome to generate antigenic diversity in tick-borne ehrlichial pathogens. Proceedings of the National Academy of Sciences, USA 98, 4130–4135.CrossRefGoogle Scholar
BUCCI, K., KASTENS, W., HOLLINGDALE, M. R., SHANKAR, A., ALPERS, M. P., KING, C. L. & KAZURA, J. W. (2000). Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1). Clinical and Experimental Immunology 122, 94–100.CrossRefGoogle Scholar
CONWAY, D. J. (1997). Natural selection on polymorphic malaria antigens and the search for a vaccine. Parasitology Today 13, 26–29.CrossRefGoogle Scholar
CONWAY, D. J., CAVANAGH, D. R., TANABE, K., ROPER, C., MIKES, Z. S., SAKIHAMA, N., BOJANG, K. A., ODUOLA, A. M. J., KREMSNER, P. G., ARNOT, D. E., GREENWOOD, B. M. & MCBRIDE, J. S. (2000a). A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nature Medicine 6, 689–692.Google Scholar
CONWAY, D. J., FANELLO, C., LLOYD, J. M., AL-JOUBORI, B. M. A.-S., BALOCH, A. H., SOMANATH, S. D., ROPER, C., ODUOLA, A. M. J., MULDER, B., POVOA, M. M., SINGH, B. & THOMAS, A. W. (2000b). Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Molecular and Biochemical Parasitology 111, 163–171.Google Scholar
CONWAY, D. J., GREENWOOD, B. M. & MCBRIDE, J. S. (1992). Longitudinal study of Plasmodium falciparum polymorphic antigens in a malaria endemic population. Infection and Immunity 60, 1122–1127.Google Scholar
CONWAY, D. J., MACHADO, R. L. D., SINGH, B., DESSERT, P., MIKES, Z. S., POVOA, M. M., ODUOLA, A. M. J. & ROPER, C. (2001). Extreme geographical fixation of variation in the Plasmodium falciparum gamete surface protein gene Pfs48/45 compared with microsatellite loci. Molecular and Biochemical Parasitology 115, 145–156.CrossRefGoogle Scholar
DRAKELEY, C. J., DURAISINGH, M. T., POVOA, M., CONWAY, D. J., TARGETT, G. A. T. & BAKER, D. A. (1996). Geographical distribution of a variant epitope of Pfs48/45, a Plasmodium falciparum transmission-blocking vaccine candidate. Molecular and Biochemical Parasitology 81, 253–257.CrossRefGoogle Scholar
ESCALANTE, A. A., LAL, A. A. & AYALA, F. J. (1998). Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum. Genetics 149, 189–202.Google Scholar
EVANS, D. T., O'CONNOR, D. H., JING, P., DZURIS, J. L., SIDNEY, J., DA SILVA, J., ALLEN, T. M., HORTON, H., VENHAM, J. E., RUDERSDORF, R. A., VOGEL, T., PAUZA, C. D., BONTROP, R. E., DEMARS, R., SETTE, A., HUGHES, A. L. & WATKINS, D. I. (1999). Virus-specific cytotoxic T lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nature Medicine 5, 1270–1276.CrossRefGoogle Scholar
FAYER, R., MORGAN, U. & UPTON, S. J. (2000). Epidemiology of Cryptosporidium: transmission, detection, and identification. International Journal for Parasitology 30, 1305–1322.CrossRefGoogle Scholar
FELGER, I., MARSHALL, V. M., REEDER, J. C., HUNT, J. A., MGONE, C. S. & BECK, H.-P. (1997). Sequence diversity and molecular evolution of the merozoite surface antigen 2 of Plasmodium falciparum. Journal of Molecular Evolution 45, 154–160.CrossRefGoogle Scholar
FERREIRA, M. U., LIU, Q., ZHOU, M., KIMURA, M., KANEKO, O., VAN THIEN, H., ISOMURA, S., TANABE, K. & KAWAMOTO, F. (1998). Stable patterns of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from southern Vietnam. Journal of Eukaryotic Microbiology 45, 131–136.CrossRefGoogle Scholar
FIDOCK, D. A., GRAS-MASSE, H., LEPERS, J. P., BRAHIMI, K., BENMOHAMED, L., MELLOUK, S., GUERIN-MARCHAND, C., LONDONO, A., RAHARIMALALA, L., MEIS, J. F., LANGSLEY, G., ROUSSILHON, C., TARTAR, A. & DRUILHE, P. (1994). Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants. Journal of Immunology 153, 190–204.Google Scholar
FU, Y.-X. & LI, W.-H. (1993). Statistical tests of neutrality of mutations. Genetics 133, 693–709.Google Scholar
FUDYK, T. C., MACLEAN, I. W., SIMONSEN, J. N., NJAGI, E. N., KIMANI, J., BRUNHAM, R. C. & PLUMMER, F. A. (1999). Genetic diversity and mosaicism at the por locus of Neisseria gonorrhoeae. Journal of Bacteriology 181, 5591–5599.Google Scholar
GILBERT, S. C., PLEBANSKI, M., GUPTA, S., MORRIS, J., COX, M., AIDOO, M., KWIATKOWSKI, D., GREENWOOD, B. M., WHITTLE, H. C. & HILL, A. V. S. (1998). Association of malaria parasite population structure, HLA, and immunological antagonism. Science 279, 1173–1177.CrossRefGoogle Scholar
GOULDER, P. J. R., BRANDER, C., TANG, Y., TREMBLAY, C., COLBERT, R. A., ADOO, M. M., ROSENBERG, E. S., NGUYEN, T., ALLEN, R., TROCHA, A., ALTFELD, M., HE, S. Q., BUNCE, M., FUNKHOUSER, R., PELTON, S. I., BURCHETT, S. K., MCINTOSH, K., KORBER, B. T. M. & WALKER, B. D. (2001). Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412, 334–338.CrossRefGoogle Scholar
GUBBELS, M.-J, KATZER, F., HIDE, G., JONGEJAN, F. & SHIELS, B. R. (2000). Generation of a mosaic pattern of diversity in the major merozoite-piroplasm surface antigen of Theileria annulata. Molecular and Biochemical Parasitology 110, 23–32.CrossRefGoogle Scholar
HALL, R., HYDE, J. E., GOMAN, M., SIMMONS, D. L., HOPE, I. A., MACKAY, M., SCAIFE, J., MERKLI, B., RICHLE, R. & STOCKER, J. (1984). Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Nature 311, 379–382.CrossRefGoogle Scholar
HAY, C. M., RUHL, D. J., BASGOZ, N. O., WILSON, C. C., BILLINGSLEY, J. M., DEPASQUALE, M. P., D'AQUILA, R. T., WOLINSKY, S. M., CRAWFORD, J. M., MONTEFIORI, D. C. & WALKER, B. D. (1999). Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection. Journal of Virology 73, 5509–5519.Google Scholar
HEHL, A. B., LEKUTIS, C., GRIGG, M. E., BRADLEY, P. J., DUBREMETZ, J.-F., ORTEGA-BARRIA, E. & BOOTHROYD, J. C. (2000). Toxoplasma gondii homologue of Plasmodium apical membrane antigen 1 is involved in invasion of host cells. Infection and Immunity 68, 7078–7076.CrossRefGoogle Scholar
HODDER, A. N., CREWTHER, P. E. & ANDERS, R. F. (2001). Specificity of the protective antibody response to apical membrane antigen 1. Infection and Immunity 69, 3286–3294.CrossRefGoogle Scholar
HOE, N. P., NAKASHIMA, K., LUKOMSKI, S., GRIGSBY, D., LIU, M., KORDARI, P. & DOU, S.-J. et al. (1999). Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves. Nature Medicine 5, 924–929.CrossRefGoogle Scholar
HOFFMAN, E. H. E., DA SILVEIRA, L. A., TONHOSOLO, R., PEREIRA, F. J. T., RIBEIRO, W. L., TONON, A. P., KAWAMOTO, F. & FERREIRA, M. U. (2001). Geographical patterns of allelic diversity in the Plasmodium falciparum malaria vaccine candidate, merozoite surface protein-2. Annals of Tropical Medicine and Parasitology 95, 117–132.CrossRefGoogle Scholar
HUGHES, M. K. & HUGHES, A. L. (1995). Natural selection on Plasmodium surface proteins. Molecular and Biochemical Parasitology 71, 99–113.CrossRefGoogle Scholar
KAPLAN, E. L., WOTTON, J. T. & JOHNSON, D. R. (2001). Dynamic epidemiology of group A streptococcal serotypes associated with pharyngitis. Lancet 358, 1334–1337.CrossRefGoogle Scholar
KELLEHER, A. D., LONG, C., HOLMES, E. C., ALLEN, R. L., WILSON, J., CONLON, C., WORKMAN, C., SHAUNAK, S., OLSON, K., GOULDER, P., BRANDER, C., OGG, G., SULLIVAN, J. S., DYER, W., JONES, I., MCMICHAEL, A. J., ROWLAND-JONES, S. & PHILLIPS, R. E. (2001). Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. Journal of Experimental Medicine 193, 375–385.CrossRefGoogle Scholar
KIMURA, M. (1983). The Neutral Theory of Molecular Evolution. Cambridge, Cambridge University Press.CrossRef
KOCKEN, C. H. M., NARUM, D. L., MASSOUGBODJI, A., AYIVI, B., DUBBELD, M. A., VAN DER WEL, A., CONWAY, D. J., SANNI, A. & THOMAS, A. W. (2000). Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1 (AMA-1), comparison with P. falciparum AMA-1, and antibody-mediated inhibition of red cell invasion. Molecular and Biochemical Parasitology 109, 147–156.Google Scholar
KREITMAN, M. (2000). Methods to detect selection in populations with application to the human. Annual Review of Genomics and Human Genetics 1, 539–559.CrossRefGoogle Scholar
KURTIS, J. D., HOLLINGDALE, M. R., LUTY, A. J. F., LANAR, D. E., KRZYCH, U. & DUFFY, P. E. (2001). Pre-erythrocytic immunity to Plasmodium falciparum: the case for an LSA-1 vaccine. Trends in Parasitology 17, 219–223.CrossRefGoogle Scholar
LI, W.-H. (1997). Molecular Evolution. Sunderland, Mass, Sinauer Associates, Inc.
MARTIENSSEN, R. A. & COLOT, V. (2001). DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science 293, 1070–1074.CrossRefGoogle Scholar
MCCOLL, D. J. & ANDERS, R. F. (1997). Conservation of structural motifs and antigenic diversity in Plasmodium falciparum merozoite surface protein-3 (MSP-3). Molecular and Biochemical Parasitology 90, 21–31.CrossRefGoogle Scholar
MCDONALD, J. H. (1994). Detecting natural selection by comparing geographic variation in protein and DNA polymorphisms. In Non-Neutral Evolution: Theories and Molecular Data (ed. GOLDING, B.), pp. 88–100. Chapman & Hall, New York & London.CrossRef
MCDONALD, J. H. & KREITMAN, M. (1991). Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654.CrossRefGoogle Scholar
MEHR, I. J., LONG, C. D., SERKIN, C. D. & SEIFERT, H. S. (2000). A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation. Genetics 154, 523–532.Google Scholar
MILLER, L. H., ROBERTS, T., SHAHABUDDIN, M. & MCCUTCHAN, T. F. (1993). Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Molecular and Biochemical Parasitology 59, 1–14.CrossRefGoogle Scholar
NEI, M. & GOJOBORI, T. (1986). Simple methods for estimating the numbers of synonymous and nonsynonymous substitutions. Molecular Biology and Evolution 3, 418–426.Google Scholar
NIELSEN, R. (2001). Statistical tests of selective neutrality in the age of genomics. Heredity 86, 641–647.CrossRefGoogle Scholar
O'DONNELL, R., DE KONING-WARD, T. F., BURT, R. A., BOCKAIRE, M., REEDER, J. C., COWMAN, A. F. & CRABB, B. S. (2001). Antibodies against merozoite surface protein (MSP)-1 19 are a major component of the invasion-inhibitory response in individuals immune to malaria. Journal of Experimental Medicine 193, 1403–1412.CrossRefGoogle Scholar
OKENU, D. M. N., THOMAS, A. W. & CONWAY, D. J. (2000). Allelic lineages of the merozoite surface protein 3 (msp3) gene in Plasmodium reichenowi and Plasmodium falciparum. Molecular and Biochemical Parasitology 109, 185–188.CrossRefGoogle Scholar
OYOK, T., ODONGA, C., MULWANI, E., ABUR, J., KADUCU, F., AKECH, M., OLANGO, J. & ONEK, P. ET AL. (2001). Outbreak of Ebola Hemorrhagic Fever – Uganda, August 2000–January 2001. Journal of the American Medical Association 285, 1010–1012.Google Scholar
OZWARA, H., KOCKEN, C. H. M., CONWAY, D. J., MWENDA, J. M. & THOMAS, A. W. (2001). Comparative analysis of Plasmodium reichenowi and P. falciparum erythrocyte-binding proteins reveals selection to maintain polymorphism in the erythrocyte-binding region of EBA-175. Molecular and Biochemical Parasitology 116, 81–84.Google Scholar
PARKHILL, J., WREN, B. W., MUNGALL, K., KETLEY, J. M., CHURCHER, C., BASHAM, D., CHILLINGWORTH, T., DAVIES, R. M., FELTWELL, T., HOLROYD, S., JAGELS, K., KARLYSHEV, A. V., MOULE, S., PALLEN, M. J., PENN, C. W., QUAIL, M. A., RAJANDREAM, M. A., RUTHERFORD, K. M., VAN VLIET, A. H. M., WHITEHEAD, S. & BARRELL, B. G. (2000). The genome sequence of the food borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403, 665–668.CrossRefGoogle Scholar
PATINO, J. A., HOLDER, A. A., MCBRIDE, J. S. & BLACKMAN, M. J. (1997). Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies. Journal of Experimental Medicine 186, 1689–1699.CrossRefGoogle Scholar
PLEBANSKI, M., LEE, E. A. M., HANNAN, C. M., FLANAGAN, K. L., GILBERT, S. C., GRAVENOR, M. B. & HILL, A. V. S. (1999). Altered peptide ligands narrow the repertoire of cellular immune responses by interfering with T-cell priming. Nature Medicine 5, 565–571.CrossRefGoogle Scholar
POLLEY, S. D. & CONWAY, D. J. (2001). Strong diversifying selection on domains of the Plasmodium falciparum Apical Membrane Antigen 1 gene. Genetics 158, 1505–1512.Google Scholar
PREISER, P. R., JARRA, W., CAPIOD, T. & SNOUNOU, G. (1999). A rhoptry-protein-associated mechanism of clonal phenotypic variation in rodent malaria. Nature 398, 618–622.CrossRefGoogle Scholar
RANNALA, B., QIU, W. G. & DYKHUIZEN, D. E. (2000). Methods for estimating gene frequencies and detecting selection in bacterial populations. Genetics 155, 499–508.Google Scholar
RICH, S. M., LICHT, M. C., HUDSON, R. R. & AYALA, F. J. (1998). Malaria's eve: Evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 95, 4425–4430.CrossRefGoogle Scholar
SIDDIQUI, W. A., TAM, L. Q., KRAMER, K. J., HUI, G. S. N., CASE, S. E., YAMAGA, K. M., CHANG, S. P., CHAN, E. B. T. & KAN, S.-C. (1987). Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proceedings of the National Academy of Sciences, USA 84, 3014–3018.CrossRefGoogle Scholar
SILVA, N. S., SILVEIRA, L. A., MACHADO, R. L. D., POVOA, M. M. & FERREIRA, M. U. (2000). Temporal and spatial distribution of the variants of merozoite surface protein-1 (MSP-1) in Plasmodium falciparum populations in Brazil. Annals of Tropical Medicine and Parasitology 94, 675–688.CrossRefGoogle Scholar
SMITH, J. D., GAMAIN, B., BARUCH, D. I. & KYES, S. (2001). Decoding the language of var genes and Plasmodium falciparum sequestration. Trends in Parasitology 17, 538–545.CrossRefGoogle Scholar
SREEVATSAN, S., PAN, X., STOCKBAUER, K. E., CONNELL, N. D., KREISWIRTH, B. N., WHITTAM, T. S. & MUSSER, J. M. (1997). Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proceedings of the National Academy of Sciences, USA 94, 9869–9874.CrossRefGoogle Scholar
STEPHENS, R. S. & LAMMEL, C. J. (2001). Chlamydia outer membrane protein discovery using genomics. Current Opinion in Microbiology 4, 16–20.CrossRefGoogle Scholar
STOTHARD, D. R., BOGUSLAWSKI, G. & JONES, R. B. (1998). Phylogenetic analysis of the Chlamydia trachomatis major outer membrane protein and examination of potential pathogenic determinants. Infection and Immunity 66, 3618–3625.Google Scholar
STRINGER, J. R. & KEELY, S. P. (2001). Genetics of surface antigen expression in Pneumocystis carinii. Infection and Immunity 69, 627–639.CrossRefGoogle Scholar
SUAREZ, C. E., FLORIN-CHRISTENSEN, M., HINES, S. A., PALMER, G. H., BROWN, W. C. & MCELWAIN, T. F. (2000). Characterization of allelic variation in the Babesia bovis merozoite surface antigen 1 (MSA-1) locus and identification of a cross-reactive inhibition-sensitive MSA-1 epitope. Infection and Immunity 68, 6865–6870.CrossRefGoogle Scholar
TAJIMA, F. (1989). Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595.Google Scholar
TANABE, K., MACKAY, M., GOMAN, M. & SCAIFE, J. G. (1987). Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. Journal of Molecular Biology 195, 273–287.CrossRefGoogle Scholar
THEISEN, M., THOMAS, A. W. & JEPSEN, S. (2001). Cloning, nucleotide sequencing and analysis of the gene encoding the glutamate-rich protein (GLURP) from Plasmodium falciparum. Molecular and Biochemical Parasitology 115, 269–273.CrossRefGoogle Scholar
TSUCHIYA, E., SUGAWARA, K., HONGO, S., MATSUZAKI, Y., MURAKI, Y., LI, Z. N. & NAKAMURA, K. (2001). Antigenic structure of the haemagglutinin of human influenza A/H2N2 virus. Journal of General Virology 82, 2475–2484.CrossRefGoogle Scholar
VAN DIJK, M. R., JANSE, C. J., THOMPSON, J., WATERS, A. P., BRAKS, J. A. M., DODEMONT, H. J., STUNNENBERG, H. G., VAN GEMERT, G.-J., SAUERWEIN, R. W. & ELING, W. (2001). A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153–164.CrossRefGoogle Scholar
VERRA, F. & HUGHES, A. L. (1999). Evidence for ancient balanced polymorphism at the apical membrane antigen-1 (AMA-1) locus of Plasmodium falciparum. Molecular and Biochemical Parasitology 105, 149–153.Google Scholar
VIDAL, N., PEETERS, V. N., MULANGA-KABEYA, C., NZILAMBI, N., ROBERTSON, D., ILUNGA, W., SEMA, H., TSHIMANGA, K., BONGO, B. & DELAPORTE, E. (2000). Unprecedented degree of human immunodeficiency virus type 1 (HIV-1) group M genetic diversity in the Democratic Republic of Congo suggests that the HIV-1 pandemic originated in Central Africa. Journal of Virology 74, 10498–10507.CrossRefGoogle Scholar
VISESHAKUL, N., KAMPER, S., BOWIE, M. V. & BARBET, A. F. (2000). Sequence and expression analysis of a surface antigen gene family of the rickettsia Anaplasma marginale. Gene 253, 45–53.CrossRefGoogle Scholar
VOLKMAN, S. K., BARRY, A. E., LYONS, E. J., NIELSEN, K. M., THOMAS, S. M., CHOI, M., THAKORE, S. S., DAY, K. P., WIRTH, D. F. & HARTL, D. L. (2001). Recent origin of Plasmodium falciparum from a single progenitor. Science 293, 482–484.CrossRefGoogle Scholar
WATTERSON, G. A. (1978). The homozygosity test of neutrality. Genetics 88, 405–417.Google Scholar
YANG, Z. & BIELAWSKI, J. P. (2000). Statistical methods for detecting molecular adaptation. Trends in Ecology and Evolution 15, 496–503.CrossRefGoogle Scholar
YANG, Z. & NIELSEN, R. (2000). Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Molecular Biology and Evolution 17, 32–43.CrossRefGoogle Scholar
YANG, Z., NIELSEN, R., GOLDMAN, N. & PEDERSEN, A.-M. K. (2000). Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155, 431–449.Google Scholar
ZANOTTO, P. M. D., GOULD, E. A., GAO, G. F., HARVEY, P. H. & HOLMES, E. C. (1996). Population dynamics of flaviviruses revealed by molecular phylogenies. Proceedings of the National Academy of Sciences, USA 93, 548–553.CrossRefGoogle Scholar
ZANOTTO, P. M. D., KALLAS, E. G., DE SOUZA, R. F. & HOLMES, E. C. (1999). Genealogical evidence for positive selection in the nef gene of HIV-1. Genetics 153, 1077–1089.Google Scholar
ZEVERING, Y., KHAMBOONRUANG, C. & GOOD, M. F. (1994). Natural amino acid polymorphisms of the circumsporozoite protein of Plasmodium falciparum abrogate specific human CD4+ T cell responsiveness. European Journal of Immunology 24, 1418–1425.CrossRefGoogle Scholar
ZHANG, J.-R. & NORRIS, S. J. (1998). Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi. Infection and Immunity 66, 3689–3697.Google Scholar
ZHU, P., VAN DER ENDE, A., FALUSH, D., BRIESKE, N., MORELLI, G., LINZ, B., POPOVIC, T., SCHUURMAN, I. G. A., ADEGBOLA, R. A., ZURTH, K., GAGNEUX, S., PLATONOV, A. E., RIOU, J. Y., CAUGANT, D. A., NICOLAS, P. & ACHTMAN, M. (2001). Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proceedings of the National Academy of Sciences, USA 98, 5234–5239.CrossRefGoogle Scholar