Hostname: page-component-59f8fd8595-tmn4r Total loading time: 0 Render date: 2023-03-22T18:51:46.143Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Toxoplasma and reaction time: role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism

Published online by Cambridge University Press:  28 August 2008

Department of Parasitology, Charles University, Viničná 7, Prague 128 44, Czech Republic
Department of Anthropology, Faculty of Humanities, Charles University, Husnikova 2075, Prague 15800, Czech Republic
Centre for Occupational and Health Psychology, School of Psychology, Cardiff University, Tower Building Park Place, CF10 3AT, UK
Department of Parasitology, Charles University, Viničná 7, Prague 128 44, Czech Republic
Department of Parasitology, Charles University, Viničná 7, Prague 128 44, Czech Republic
Central Medical Psychology Department, Central Military Hospital, U vojenské nemocnice 1200, Prague 169 02, Czech Republic
Institute of Haematology and Blood Transfusion, U nemocnice 1, 120 00 Prague, Czech Republic
Institute of Haematology and Blood Transfusion, U nemocnice 1, 120 00 Prague, Czech Republic
Transfusion Unit, General Teaching Hospital, K Interně 640, Prague 156 00, Czech Republic
Department of Parasitology, Charles University, Viničná 7, Prague 128 44, Czech Republic
*Corresponding author: Department of Parasitology, Charles University, Viničná 7, CZ-128 44 Praha 2, Czech Republic. Tel: +420 221951821. Fax: +420 224919704. E-mail:


The RhD protein which is the RHD gene product and a major component of the Rh blood group system carries the strongest blood group immunogen, the D-antigen. This antigen is absent in a significant minority of the human population (RhD-negatives) due to RHD deletion or alternation. The origin and persistence of this RhD polymorphism is an old evolutionary enigma. Before the advent of modern medicine, the carriers of the rarer allele (e.g. RhD-negative women in the population of RhD-positives or RhD-positive men in the population of RhD-negatives) were at a disadvantage as some of their children (RhD-positive children born to pre-immunized RhD-negative mothers) were at a higher risk of foetal or newborn death or health impairment from haemolytic disease. Therefore, the RhD-polymorphism should be unstable, unless the disadvantage of carriers of the locally less abundant allele is counterbalanced by, for example, higher viability of the heterozygotes. Here we demonstrated for the first time that among Toxoplasma-free subjects the RhD-negative men had faster reaction times than Rh-positive subjects and showed that heterozygous men with both the RhD plus and RhD minus alleles were protected against prolongation of reaction times caused by infection with the common protozoan parasite Toxoplasma gondii. Our results suggest that the balancing selection favouring heterozygotes could explain the origin and stability of the RhD polymorphism. Moreover, an unequal prevalence of toxoplasmosis in different countries could explain pronounced differences in frequencies of RhD-negative phenotype in geographically distinct populations.

Original Articles
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



Allison, A. C. (1954). The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 48, 312318.CrossRefGoogle ScholarPubMed
Berdoy, M., Webster, J. P. and Macdonald, D. W. (2000). Fatal attraction in rats infected with Toxoplasma gondii. Proceedings of the Royal Society of London, B 267, 15911594.CrossRefGoogle ScholarPubMed
Biver, S., Scohy, S., Szpirer, J., Szpirer, C., Andre, B. and Marini, A. M. (2006). Physiological role of the putative ammonium transporter RhCG in the mouse. Transfusion Clinique et Biologique 13, 167168.CrossRefGoogle ScholarPubMed
Courtiere, A., Hardouin, J., Goujon, A., Vidal, F. and Hasbroucq, T. (2003). Selective effects of low-dose dopamine D-1 and D-2 receptor antagonists on rat information processing. Behavioural Pharmacology 14, 589598.CrossRefGoogle Scholar
Daniels, G. (2002). Human Blood Groups. Blackwell Publishers, Oxford, UK.CrossRefGoogle Scholar
Dubey, J. P., Rollor, E. A., Smith, K., Kwok, O. C. H. and Thulliez, P. (1997). Low seroprevalence of Toxoplasma gondii in feral pigs from a remote island lacking cats. Journal of Parasitology 83, 839841.CrossRefGoogle ScholarPubMed
Fisher, R. A., Race, R. R. and Taylor, G. L. (1944). Mutation and the Rhesus reaction. Nature, London 153, 106.CrossRefGoogle Scholar
Feldman, M. W., Nabholz, M. and Bodmer, W. F. (1969). Evolution of the Rh polymorphism: A model for the interaction of incompatibility, reproductive compensation and heterozygote advantage. Journal of Human Genetics 21, 171193.Google ScholarPubMed
Flegr, J. (2007). Effects of Toxoplasma on human behavior. Schizophrenia Bulletin 33, 757760.CrossRefGoogle ScholarPubMed
Flegr, J., Havlíček, J., Kodym, P., Malý, M. and Šmahel, Z. (2002). Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. Bmc Infectious Diseases 2, art-11.CrossRefGoogle ScholarPubMed
Flegr, J., Kodym, P. and Tolarová, V. (2000). Correlation of duration of latent Toxoplasma gondii infection with personality changes in women. Biological Psychology 53, 5768.CrossRefGoogle ScholarPubMed
Flegr, J., Lindová, J. and Kodym, P. (2008). Sex-dependent toxoplasmosis-associated differences in testosterone concentration in humans. Parasitology 135, 427431.CrossRefGoogle ScholarPubMed
Flegr, J., Preiss, M., Klose, J., Havlíček, J., Vitaková, M. and Kodym, P. (2003). Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii. Dopamine, a missing link between schizophrenia and toxoplasmosis? Biological Psychology 63, 253268.CrossRefGoogle Scholar
Flegr, J., Zitková, S., Kodym, P. and Frynta, D. (1996). Induction of changes in human behaviour by the parasitic protozoan Toxoplasma gondii. Parasitology 113, 4954.CrossRefGoogle ScholarPubMed
Haldane, J. B. S. (1942). Selection against heterozygosis in Man. Eugenics 11, 333340.CrossRefGoogle Scholar
Havlíček, J., Gašová, Z., Smith, A. P., Zvára, K. and Flegr, J. (2001). Decrease of psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis. Parasitology 122, 515520.CrossRefGoogle ScholarPubMed
Havlicek, J., Roberts, S. C. and Flegr, J. (2005). Women's preference for dominant male odour: effects of menstrual cycle and relationship status. Biology Letters 1, 256259.CrossRefGoogle ScholarPubMed
Hodková, H., Kodym, P. and Flegr, J. (2007). Poorer results of mice with latent toxoplasmosis in learning tests: impaired learning processes or the novelty discrimination mechanism? Parasitology 134, 13291337.CrossRefGoogle ScholarPubMed
Hogben, L. (1943) Mutation and the Rhesus reaction. Nature, London 152, 721722.CrossRefGoogle Scholar
Kahkonen, S., Ahveninen, J., Pekkonen, E., Kaakkola, S., Huttunen, J., Ilmoniemi, R. J. and Jaaskelainen, I. P. (2002). Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study. Clinical Neurophysiology 113, 18941902.CrossRefGoogle ScholarPubMed
Kaňková, Š. and Flegr, J. (2007). Longer pregnancy and slower fetal development in women with latent “asymptomatic” toxoplasmosis. BMC Infectious Diseases 7, art-114.CrossRefGoogle ScholarPubMed
Kaňková, Š., Kodym, P., Frynta, D., Vavřinová, R., Kuběna, A. and Flegr, J. (2007). Influence of latent toxoplasmosis on the secondary sex ratio in mice. Parasitology 134, 17091718.CrossRefGoogle ScholarPubMed
Kustu, S. and Inwood, W. (2006). Biological gas channels for NH3 and CO(2): evidence that Rh (rhesus) proteins are CO(2) channels. Transfusion Clinique et Biologique 13, 103110.CrossRefGoogle Scholar
Hogben, L. (1943). Mutation and the Rhesus reaction. Nature, London 152, 721722.CrossRefGoogle Scholar
Kolbekova, P., Kourbatova, E., Novotna, M., Kodym, P. and Flegr, J. (2007). New and old risk-factors for Toxoplasma gondii infection: prospective cross-sectional study among military personnel in the Czech Republic. Clinical Microbiology and Infection 13, 10121017.CrossRefGoogle ScholarPubMed
Li, C. C. (1953). Is the Rh facing a cross-road? A critique of the compensation effect. American Naturalist 87, 257261.CrossRefGoogle Scholar
Lindová, J., Novotná, M., Havlíček, J., Jozífková, E., Skallová, A., Kolbeková, P., Hodný, Z., Kodym, P. and Flegr, J. (2006). Gender differences in behavioural changes induced by latent toxoplasmosis. International Journal for Parasitology 36, 14851492.CrossRefGoogle ScholarPubMed
Markell, E. K., John, D. T. and Krotoski, W. A. (1999). Markell and Voge's Medical Parasitology, 8th Edn.W.B. Saunders and Company, Philadelphia, PA, USA.Google Scholar
Nieoullon, A. (2002). Dopamine and the regulation of cognition and attention. Progress in Neurobioogy 67, 5383.CrossRefGoogle ScholarPubMed
Novotná, M., Hanušová, J., Klose, J., Preiss, M., Havlicek, J., Roubalová, K. and Flegr, J. (2005). Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host. BMC Infectious Diseases 5, art-54.CrossRefGoogle ScholarPubMed
Pokorný, J., Fruhbauer, Z., Poledňáková, S., Sýkora, J., Zástěra, M. and Fialová, D. (1989). Stanoveni antitoxoplasmickych protilatek IgG metodou ELISA (Assessment of antitoxoplasmatic IgG antibodies with the ELISA method). Ceskoslovenska Epidemiologie 38, 355361.Google Scholar
Remington, J. S. and Krahenbuhl, J. L. (1982). Immunology of Toxoplasma gondii. In Immunology of Human Infection, Part II (ed. Nahmias, A. J. and O'Reilly, J.), pp. 327371. Plenum Publishing Corporation, New York, USA.CrossRefGoogle Scholar
Rihet, P., Possamai, C. A., Micallef-Roll, J., Blin, O. and Hasbroucq, T. (2002). Dopamine and human information processing: a reaction-time analysis of the effect of levodopa in healthy subjects. Psychopharmacology 163, 6267.CrossRefGoogle ScholarPubMed
Roberts, L. S. and Janovy, J. Jr. (2000). Gerald S. Schmidt & Larry S. Roberts' Foundations of Parasitology, 6th Edn.McGraw-Hill Companies, Inc, Boston, l MA, USA.Google Scholar
Roever-Bonnet, H. D. (1972). Toxoplasmosis in tropical Africa. Tropical and Geographical Medicine 24, 713.Google ScholarPubMed
Skallová, A., Novotná, M., Kolbeková, P., Gašová, Z., Veselý, V. and Flegr, J. (2005). Decreased level of novelty seeking in blood donors infected with Toxoplasma. Neuroendocrinology Letters 26, 480486.Google ScholarPubMed
Skallová, A., Kodym, P., Frynta, D. and Flegr, J. (2006). The role of dopamine in Toxoplasma-induced behavioural alterations in mice: an ethological and ethopharmacological study. Parasitology 133, 525535.CrossRefGoogle ScholarPubMed
Smith, A. P., Tyrrell, D. A. J., Al-Nakib, W., Barrow, P. G., Higgins, P. G., Leekam, S. and Trickett, S. (1989). Effects and after-effects of the common cold and influenza on human performance. Neuropsychobiology 21, 9093.CrossRefGoogle ScholarPubMed
Stibbs, H. H. (1985). Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Annals of Tropical Medicine and Parasitology 79, 153157.CrossRefGoogle ScholarPubMed
Torrey, E. F. and Yolken, R. H. (1995). Could schizophrenia be a viral zoonosis transmitted from house cats? Schizophrenia Bulletin 21, 167171.CrossRefGoogle ScholarPubMed
Wagner, F. F. and Flegel, W. A. (2000). RHD gene deletion occurred in the Rhesus box. Blood 95, 36623668.Google ScholarPubMed
Warren, J. and Sabin, A. B. (1942). The complement fixation reaction in toxoplasmic infection. Proceedings of the Society for Experimental Biology and Medicine 51, 1116.CrossRefGoogle Scholar
Yereli, K., Balcioglu, I. C. and Ozbilgin, A. (2006). - Is Toxoplasma gondii a potential risk for traffic accidents in Turkey? Forensic Science International. 163, 3437.CrossRefGoogle ScholarPubMed