Abstract
What stops parasites becoming ever more virulent? Conventional wisdom and most parasite-centred models of the evolution of virulence suppose that risk of host (and, hence, parasite) death imposes selection against more virulent strains. Here we selected for high and low virulence within each of two clones of the rodent malaria parasite Plasmodium chabaudi on the basis of between-host differences in a surrogate measure of virulence--loss of live weight post-infection. Despite imposing strong selection for low virulence which mimicked 50-75% host mortality, the low virulence lines increased in virulence as much as the high virulence lines. Thus, artificial selection on between-host differences in virulence was unable to counteract natural selection for increased virulence caused by within-host selection processes. The parasite's asexual replication rate and number of sexual transmission forms also increased in all lines, consistent with evolutionary models explaining high virulence. An upper bound to virulence, though not the asexual replication rate, was apparent, but this bound was not imposed by host mortality. Thus, we found evidence of the factors assumed to drive evolution of increased virulence, but not those thought to counter this selection.
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- Alger N. E., Branton M., Harant J., Silverman P. H. Plasmodium berghei NK65 in the inbred A-J mouse: variations in virulence of P. berghei demes. J Protozool. 1971 Nov;18(4):598–601. doi: 10.1111/j.1550-7408.1971.tb03382.x. [DOI] [PubMed] [Google Scholar]
- Anderson R. M., May R. M. Coevolution of hosts and parasites. Parasitology. 1982 Oct;85(Pt 2):411–426. doi: 10.1017/s0031182000055360. [DOI] [PubMed] [Google Scholar]
- Anderson R. M., May R. M., Gupta S. Non-linear phenomena in host-parasite interactions. Parasitology. 1989;99 (Suppl):S59–S79. doi: 10.1017/s0031182000083426. [DOI] [PubMed] [Google Scholar]
- Antia R., Nowak M. A., Anderson R. M. Antigenic variation and the within-host dynamics of parasites. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):985–989. doi: 10.1073/pnas.93.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baruch D. I., Pasloske B. L., Singh H. B., Bi X., Ma X. C., Feldman M., Taraschi T. F., Howard R. J. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell. 1995 Jul 14;82(1):77–87. doi: 10.1016/0092-8674(95)90054-3. [DOI] [PubMed] [Google Scholar]
- Berendt A. R., Simmons D. L., Tansey J., Newbold C. I., Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature. 1989 Sep 7;341(6237):57–59. doi: 10.1038/341057a0. [DOI] [PubMed] [Google Scholar]
- Brannan L. R., McLean S. A., Phillips R. S. Antigenic variants of Plasmodium chabaudi chabaudi AS and the effects of mosquito transmission. Parasite Immunol. 1993 Mar;15(3):135–141. doi: 10.1111/j.1365-3024.1993.tb00593.x. [DOI] [PubMed] [Google Scholar]
- Brannan L. R., Turner C. M., Phillips R. S. Malaria parasites undergo antigenic variation at high rates in vivo. Proc Biol Sci. 1994 Apr 22;256(1345):71–75. doi: 10.1098/rspb.1994.0051. [DOI] [PubMed] [Google Scholar]
- Bremermann H. J., Pickering J. A game-theoretical model of parasite virulence. J Theor Biol. 1983 Feb 7;100(3):411–426. doi: 10.1016/0022-5193(83)90438-1. [DOI] [PubMed] [Google Scholar]
- Brown K. N., Brown I. N. Immunity to malaria: antigenic variation in chronic infections of Plasmodium knowlesi. Nature. 1965 Dec 25;208(5017):1286–1288. doi: 10.1038/2081286a0. [DOI] [PubMed] [Google Scholar]
- Buckling A. G., Taylor L. H., Carlton J. M., Read A. F. Adaptive changes in Plasmodium transmission strategies following chloroquine chemotherapy. Proc Biol Sci. 1997 Apr 22;264(1381):553–559. doi: 10.1098/rspb.1997.0079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burroughs N. J., Rand D. A. Dynamics of T-cell antagonism: enhanced viral diversity and survival. Proc Biol Sci. 1998 Mar 22;265(1395):529–535. doi: 10.1098/rspb.1998.0327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CONTACOS P. G., ELDER H. A., COATNEY G. R., GENTHER C. Man to man transfer of two strains of Plasmodium cynomolgi by mosquito bite. Am J Trop Med Hyg. 1962 Mar;11:186–193. doi: 10.4269/ajtmh.1962.11.186. [DOI] [PubMed] [Google Scholar]
- Chin W., Contacos P. G., Collins W. E., Jeter M. H., Alpert E. Experimental mosquito-transmission of Plasmodium knowlesi to man and monkey. Am J Trop Med Hyg. 1968 May;17(3):355–358. doi: 10.4269/ajtmh.1968.17.355. [DOI] [PubMed] [Google Scholar]
- Clayton D. H., Tompkins D. M. Ectoparasite virulence is linked to mode of transmission. Proc Biol Sci. 1994 Jun 22;256(1347):211–217. doi: 10.1098/rspb.1994.0072. [DOI] [PubMed] [Google Scholar]
- David P. H., Hudson D. E., Hadley T. J., Klotz F. W., Miller L. H. Immunization of monkeys with a 140 kilodalton merozoite surface protein of Plasmodium knowlesi malaria: appearance of alternate forms of this protein. J Immunol. 1985 Jun;134(6):4146–4152. [PubMed] [Google Scholar]
- Day J. F., Edman J. D. Malaria renders mice susceptible to mosquito feeding when gametocytes are most infective. J Parasitol. 1983 Feb;69(1):163–170. [PubMed] [Google Scholar]
- Dearsly A. L., Sinden R. E., Self I. A. Sexual development in malarial parasites: gametocyte production, fertility and infectivity to the mosquito vector. Parasitology. 1990 Jun;100(Pt 3):359–368. doi: 10.1017/s0031182000078628. [DOI] [PubMed] [Google Scholar]
- Ebert D. Experimental evolution of parasites. Science. 1998 Nov 20;282(5393):1432–1435. doi: 10.1126/science.282.5393.1432. [DOI] [PubMed] [Google Scholar]
- Ebert D., Herre E. A. The evolution of parasitic diseases. Parasitol Today. 1996 Mar;12(3):96–101. doi: 10.1016/0169-4758(96)80668-5. [DOI] [PubMed] [Google Scholar]
- Ebert D. Virulence and local adaptation of a horizontally transmitted parasite. Science. 1994 Aug 19;265(5175):1084–1086. doi: 10.1126/science.265.5175.1084. [DOI] [PubMed] [Google Scholar]
- Frank S. A. Models of parasite virulence. Q Rev Biol. 1996 Mar;71(1):37–78. doi: 10.1086/419267. [DOI] [PubMed] [Google Scholar]
- Futuyma D. J. The uses of evolutionary biology. Science. 1995 Jan 6;267(5194):41–42. doi: 10.1126/science.7809608. [DOI] [PubMed] [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. Association of malaria parasite population structure, HLA, and immunological antagonism. Science. 1998 Feb 20;279(5354):1173–1177. doi: 10.1126/science.279.5354.1173. [DOI] [PubMed] [Google Scholar]
- Gilks C. F., Walliker D., Newbold C. I. Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi--a rodent malaria model. Parasite Immunol. 1990 Jan;12(1):45–64. doi: 10.1111/j.1365-3024.1990.tb00935.x. [DOI] [PubMed] [Google Scholar]
- Gravenor M. B., Kwiatkowski D. An analysis of the temperature effects of fever on the intra-host population dynamics of Plasmodium falciparum. Parasitology. 1998 Aug;117(Pt 2):97–105. doi: 10.1017/s0031182098002893. [DOI] [PubMed] [Google Scholar]
- Gravenor M. B., McLean A. R., Kwiatkowski D. The regulation of malaria parasitaemia: parameter estimates for a population model. Parasitology. 1995 Feb;110(Pt 2):115–122. doi: 10.1017/s0031182000063861. [DOI] [PubMed] [Google Scholar]
- Gravenor M. B., van Hensbroek M. B., Kwiatkowski D. Estimating sequestered parasite population dynamics in cerebral malaria. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7620–7624. doi: 10.1073/pnas.95.13.7620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenwood B., Marsh K., Snow R. Why do some African children develop severe malaria? Parasitol Today. 1991 Oct;7(10):277–281. doi: 10.1016/0169-4758(91)90096-7. [DOI] [PubMed] [Google Scholar]
- Haydon D. T., Woolhouse M. E. Immune avoidance strategies in RNA viruses: fitness continuums arising from trade-offs between immunogenicity and antigenic variability. J Theor Biol. 1998 Aug 21;193(4):601–612. doi: 10.1006/jtbi.1998.0726. [DOI] [PubMed] [Google Scholar]
- Hellriegel B. Modelling the immune response to malaria with ecological concepts: short-term behaviour against long-term equilibrium. Proc Biol Sci. 1992 Dec 22;250(1329):249–256. doi: 10.1098/rspb.1992.0156. [DOI] [PubMed] [Google Scholar]
- Herre E. A. Population structure and the evolution of virulence in nematode parasites of fig wasps. Science. 1993 Mar 5;259(5100):1442–1445. doi: 10.1126/science.259.5100.1442. [DOI] [PubMed] [Google Scholar]
- Hetzel C., Anderson R. M. The within-host cellular dynamics of bloodstage malaria: theoretical and experimental studies. Parasitology. 1996 Jul;113(Pt 1):25–38. doi: 10.1017/s0031182000066245. [DOI] [PubMed] [Google Scholar]
- Hommel M., David P. H., Oligino L. D. Surface alterations of erythrocytes in Plasmodium falciparum malaria. Antigenic variation, antigenic diversity, and the role of the spleen. J Exp Med. 1983 Apr 1;157(4):1137–1148. doi: 10.1084/jem.157.4.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hudson D. E., Wellems T. E., Miller L. H. Molecular basis for mutation in a surface protein expressed by malaria parasites. J Mol Biol. 1988 Oct 5;203(3):707–714. doi: 10.1016/0022-2836(88)90204-5. [DOI] [PubMed] [Google Scholar]
- James S. P., Nicol W. D., Shute P. G. Clinical and Parasitological Observations on Induced Malaria: (Section of Tropical Diseases and Parasitology). Proc R Soc Med. 1936 Jun;29(8):879–894. [PMC free article] [PubMed] [Google Scholar]
- Kimura M., Crow J. F. Effect of overall phenotypic selection on genetic change at individual loci. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6168–6171. doi: 10.1073/pnas.75.12.6168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klotz F. W., Hudson D. E., Coon H. G., Miller L. H. Vaccination-induced variation in the 140 kD merozoite surface antigen of Plasmodium knowlesi malaria. J Exp Med. 1987 Feb 1;165(2):359–367. doi: 10.1084/jem.165.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwiatkowski D., Bate C. A., Scragg I. G., Beattie P., Udalova I., Knight J. C. The malarial fever response--pathogenesis, polymorphism and prospects for intervention. Ann Trop Med Parasitol. 1997 Jul;91(5):533–542. doi: 10.1080/00034989760905. [DOI] [PubMed] [Google Scholar]
- Kwiatkowski D., Nowak M. Periodic and chaotic host-parasite interactions in human malaria. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5111–5113. doi: 10.1073/pnas.88.12.5111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipsitch M., Moxon E. R. Virulence and transmissibility of pathogens: what is the relationship? Trends Microbiol. 1997 Jan;5(1):31–37. doi: 10.1016/S0966-842X(97)81772-6. [DOI] [PubMed] [Google Scholar]
- May R. M., Anderson R. M. Epidemiology and genetics in the coevolution of parasites and hosts. Proc R Soc Lond B Biol Sci. 1983 Oct 22;219(1216):281–313. doi: 10.1098/rspb.1983.0075. [DOI] [PubMed] [Google Scholar]
- McKenzie F. E., Bossert W. H. The dynamics of Plasmodium falciparum blood-stage infection. J Theor Biol. 1997 Sep 7;188(1):127–140. doi: 10.1006/jtbi.1997.0478. [DOI] [PubMed] [Google Scholar]
- McLean S. A., Pearson C. D., Phillips R. S. Plasmodium chabaudi: antigenic variation during recrudescent parasitaemias in mice. Exp Parasitol. 1982 Dec;54(3):296–302. doi: 10.1016/0014-4894(82)90038-8. [DOI] [PubMed] [Google Scholar]
- Ockenhouse C. F., Ho M., Tandon N. N., Van Seventer G. A., Shaw S., White N. J., Jamieson G. A., Chulay J. D., Webster H. K. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991 Jul;164(1):163–169. doi: 10.1093/infdis/164.1.163. [DOI] [PubMed] [Google Scholar]
- Ockenhouse C. F., Klotz F. W., Tandon N. N., Jamieson G. A. Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3175–3179. doi: 10.1073/pnas.88.8.3175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ockenhouse C. F., Tandon N. N., Magowan C., Jamieson G. A., Chulay J. D. Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science. 1989 Mar 17;243(4897):1469–1471. doi: 10.1126/science.2467377. [DOI] [PubMed] [Google Scholar]
- Read A. F. The evolution of virulence. Trends Microbiol. 1994 Mar;2(3):73–76. doi: 10.1016/0966-842x(94)90537-1. [DOI] [PubMed] [Google Scholar]
- Roberts D. D., Sherwood J. A., Spitalnik S. L., Panton L. J., Howard R. J., Dixit V. M., Frazier W. A., Miller L. H., Ginsburg V. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature. 1985 Nov 7;318(6041):64–66. doi: 10.1038/318064a0. [DOI] [PubMed] [Google Scholar]
- Roberts D. J., Craig A. G., Berendt A. R., Pinches R., Nash G., Marsh K., Newbold C. I. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992 Jun 25;357(6380):689–692. doi: 10.1038/357689a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. D., Chitnis C. E., Craig A. G., Roberts D. J., Hudson-Taylor D. E., Peterson D. S., Pinches R., Newbold C. I., Miller L. H. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell. 1995 Jul 14;82(1):101–110. doi: 10.1016/0092-8674(95)90056-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevenson M. M., Lyanga J. J., Skamene E. Murine malaria: genetic control of resistance to Plasmodium chabaudi. Infect Immun. 1982 Oct;38(1):80–88. doi: 10.1128/iai.38.1.80-88.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su X. Z., Heatwole V. M., Wertheimer S. P., Guinet F., Herrfeldt J. A., Peterson D. S., Ravetch J. A., Wellems T. E. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell. 1995 Jul 14;82(1):89–100. doi: 10.1016/0092-8674(95)90055-1. [DOI] [PubMed] [Google Scholar]
- Taylor-Robinson A. W. Immunoregulation of malarial infection: balancing the vices and virtues. Int J Parasitol. 1998 Jan;28(1):135–148. doi: 10.1016/s0020-7519(97)00173-2. [DOI] [PubMed] [Google Scholar]
- Taylor-Robinson A. W. Regulation of immunity to malaria: valuable lessons learned from murine models. Parasitol Today. 1995 Sep;11(9):334–342. doi: 10.1016/0169-4758(95)80186-3. [DOI] [PubMed] [Google Scholar]
- Taylor L. H., Read A. F. Why so few transmission stages? Reproductive restraint by malaria parasites. Parasitol Today. 1997 Apr;13(4):135–140. doi: 10.1016/s0169-4758(97)89810-9. [DOI] [PubMed] [Google Scholar]
- Taylor L. H., Walliker D., Read A. F. Mixed-genotype infections of malaria parasites: within-host dynamics and transmission success of competing clones. Proc Biol Sci. 1997 Jun 22;264(1383):927–935. doi: 10.1098/rspb.1997.0128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor L. H., Walliker D., Read A. F. Mixed-genotype infections of the rodent malaria Plasmodium chabaudi are more infectious to mosquitoes than single-genotype infections. Parasitology. 1997 Aug;115(Pt 2):121–132. doi: 10.1017/s0031182097001145. [DOI] [PubMed] [Google Scholar]
- White N. J., Ho M. The pathophysiology of malaria. Adv Parasitol. 1992;31:83–173. doi: 10.1016/s0065-308x(08)60021-4. [DOI] [PubMed] [Google Scholar]
- Williams G. C., Nesse R. M. The dawn of Darwinian medicine. Q Rev Biol. 1991 Mar;66(1):1–22. doi: 10.1086/417048. [DOI] [PubMed] [Google Scholar]
- Yap G. S., Stevenson M. M. Blood transfusion alters the course and outcome of Plasmodium chabaudi AS infection in mice. Infect Immun. 1994 Sep;62(9):3761–3765. doi: 10.1128/iai.62.9.3761-3765.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoeli M., Hargreaves B., Carter R., Walliker D. Sudden increase in virulence in a strain of Plasmodium berghei yoelii. Ann Trop Med Parasitol. 1975 Jun;69(2):173–178. doi: 10.1080/00034983.1975.11686998. [DOI] [PubMed] [Google Scholar]