Evolutionary History and Population Genetics of Human Malaria Parasites

Martine Zilversmit; Daniel L. Hartl

doi:10.1128/9781555817558.ch7

Chapter 7 : Evolutionary History and Population Genetics of Human Malaria Parasites

Authors: Martine Zilversmit¹, Daniel L. Hartl²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138; 2: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138

Content Type: Monograph

Publication Year: 2005

Category: Microbial Genetics and Molecular Biology

Book DOI: 10.1128/9781555817558

Chapter DOI: 10.1128/9781555817558.ch7

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Evolutionary History and Population Genetics of Human Malaria Parasites, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817558/9781555813307_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555817558/9781555813307_Chap07-2.gif

Abstract:

The central theme of this chapter is the molecular evolution of species of the genus Plasmodium—the experimental methods, conclusions, and confounding elements peculiar to Plasmodium. While one section of the chapter is a brief summary of studies on the evolutionary history of Plasmodium and related organisms, another is a summary of the molecular population genetics of contemporary world populations of the two most virulent human malaria parasites. In addition to humans, Plasmodium parasites infect a range of vertebrate hosts, including birds, lizards, rodents, and nonhuman primates. Malaria has also been found in African rodents, and many of the Plasmodium species have been adapted to laboratory mice and rats and used as models for human malarias. Plasmodium ovale and P. malariae cause the rarest and least virulent forms of malaria. Population studies of P. falciparum and P. vivax, however, have already yielded unexpected results, paradoxical conclusions, and questions calling for additional research. Genome-level research has made it possible to explore malaria evolution in greater depth and rigor to help complete the picture. These changes have come through malaria parasite genome projects (for P. falciparum, P. vivax, P. yoelii, and P. reichenowi) and their associated databases, access to automated DNA sequencers in most modern laboratories, an increasingly sophisticated understanding of the unusual molecular biology and evolution of the parasites, and improvements in methods of statistical inference from DNA sequence differences within and among populations.

Citation: Zilversmit M, Hartl D. 2005. Evolutionary History and Population Genetics of Human Malaria Parasites, p 95-109. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch7

Highlighted Text: Show | Hide

Full text loading...

Figures

Evolutionary History and Population Genetics of Human Malaria Parasites

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817558.chap7-1,webId=/content/author/10.1128/9781555817558.chap7-1,properties={foaf_givenname=Martine, foaf_name=Martine Zilversmit, foaf_surname=Zilversmit, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817558.chap7-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817558.chap7-2,webId=/content/author/10.1128/9781555817558.chap7-2,properties={foaf_givenname=Daniel L., foaf_name=Daniel L. Hartl, foaf_surname=Hartl, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817558.chap7-aff2]]}]]

/content/10.1128/9781555817558.chap7.fig7-1

FIGURE 1

Summary phylogenetic tree showing the relationship between malaria parasites of mammals. Note that primate Plasmodium species are monophyletic, with the exception of the P. falciparum-P. reichenowi pairing, which is outside both rodent and primate clades. Rodent and primate parasites form monophyletic groups. Branch lengths are not proportional; only nodes with statistical support of ≥85% are shown ( Escalante et al., 1995 ; Perkins and Schall, 2002 ; Vargas-Serrato et al., 2003 ).

10.1128/9781555817558/fig7-1_thmb.gif

10.1128/9781555817558/fig7-1.gif

FIGURE 1

/content/10.1128/9781555817558.chap7.fig7-2

FIGURE 2

Unrooted tree showing the relationship of infrakingdom Alveolata (Plasmodium) to other infrakingdoms (including parasites and genomic models) within the domain Eukarya ( Cavalier-Smith, 1991 , 2004 ; Cavalier-Smith and Chao, 2003 ; Baldauf et al., 2000 ; Hedges, 2002 ; Leander et al., 2003 ).The dotted line indicates the possible sister relationship of Plantae to some protist groups ( Bastien et al., 2004 ). Branch lengths are not proportional; only nodes showing statistical support of ≥85% are included.

10.1128/9781555817558/fig7-2_thmb.gif

10.1128/9781555817558/fig7-2.gif

FIGURE 2

/content/10.1128/9781555817558.chap7.fig7-3

FIGURE 3

Placement of the order Haemosporidia with the phylum Apicomplexa and relation of Apicomplexa within Alveolata. The infrakingdom Discicristata is the sister group to Alveolata and includes several well-studied parasites. Branch lengths are not proportional; only nodes showing statistical support of ≥85% are included ( Baldauf et al., 2000 ).

10.1128/9781555817558/fig7-3_thmb.gif

10.1128/9781555817558/fig7-3.gif

FIGURE 3

/content/10.1128/9781555817558.chap7.fig7-4

FIGURE 4

An unrooted neighbor-joining tree showing the relationships between nine P. falciparum populations. Only nodes with a bootstrap value of >75% are shown. Note that the African isolates (Zimbabwe, Congo, Uganda) from an area of high transmission show a large overall difference from the other isolates, but the relationship of the individual isolates cannot be distinguished with any statistical certainty. However, in South America, the Colombian and Bolivian-Brazilian isolates show a greater distance from each other than even overall distances from isolates from elsewhere in the world. (Figure adapted from Anderson et al., 2000 .)

10.1128/9781555817558/fig7-4_thmb.gif

10.1128/9781555817558/fig7-4.gif

FIGURE 4

References

/content/book/10.1128/9781555817558.chap7

1. Anderson, T. J. C.,, B. Haubold,, J.T. Williams,, J. G. Estrada-Franco,, L. Richardson,, R. Mollinedo,, M. Bockarie,, J. Mokili,, S. Mharakurwa,, N. French,, J. Whitworth,, I. D. Velez,, A. H. Brockman,, F. Nosten,, M. U. Ferreira,, and K. P. Day. 2000. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol. Biol. Evol. 17: 1467– 1482.

2. Baldauf, S. L.,, A. J. Roger,, I. Wenk-Siefert,, and W. F. Doolittle. 2000. A kingdom-level phylogeny of eukaryotes on combined protein data. Science 290: 972– 977.

3. Barry, A. E.,, A. Leliwa,, M. Choi,, K. M. Nielsen,, D. L. Hartl,, and K. P. Day. 2003. DNA sequence artifacts and the estimation of time to the most recent common ancestor (TMRCA) of Plasmodium falciparum. Mol. Biochem. Parasitol . 130: 143– 147.

4. Bastien, O.,, S. Lespinats,, S. Roy,, K. Metayer,, B. Fertil,, J. J. Codani,, and E. Marechal. 2004. Analysis of the compositional biases in Plasmodium falciparum genome and proteome using Arabidopsis thaliana as a reference. Gene 336: 163– 173.

5. Cavalier-Smith, T., 1991. Cell diversification in heterotrophic flagellates, p. 113– 131. In D. J. Patterson, and J. Larsen (ed.), The Biology of Freeliving Heterotrophic Flagellates. Oxford University Press, New York, N.Y.

6. Cavalier-Smith, T. 2004. Only six kingdoms of life. Proc. R. Soc. Lond. B Biol. Sci. 271: 1251– 1262.

7. Cavalier-Smith, T.,, and E. E.-Y. Chao. 2003. Phylogeny of choanozoa, apusozoa, and other protozoa and early eukaryote megaevolution. J. Mol. Evol. 56: 540– 563.

8. Coatney, G. R.,, W. E. Collins,, M. Warren,, and P. G. Contacos. 1971. The Primate Malarias. U.S. Department of Health, Education and Welfare, Bethesda, Md.

9. Conway, D. J. 1997. Natural selection on polymorphic malaria antigens and the search for a vaccine. Parasitol. Today 13: 26– 29.

10. Conway, D. J.,, C. Roper,, A. M. Oduola,, D. E. Arnot,, P. G. Kremsner,, M. P. Grobusch,, C. F. Curtis,, and B. M. Greenwood. 1999. High recombination rate in natural populations of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 96: 4506– 4511.

11. Conway, D. J.,, C. Fanello,, J. M. Lloyd,, B. M. Al- Joubori,, A. H. Baloch,, S. D. Somanath,, C. Roper,, A. M. Oduola,, B. Mulder,, M. M. Povoa,, B. Singh,, and A. W. Thomas. 2000. Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol. Biochem. Parasitol. 111: 163– 171.

12. Corredor, V.,, and V. Enea. 1993. Plasmodial ribosomal RNA as phylogenetic probe: a cautionary note. Mol. Biol. Evol. 10: 924– 926.

13. Coulson, R. M.,, N. Hall,, and C. A. Ouzounis. 2004. Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum. Genome Res. 14: 1548– 1554.

14. Drakeley C. J.,, M. T. Duraisingh,, M. Povoa,, D. J. Conway,, G. A. Targett,, and D. A. Baker. 1996. Geographical distribution of a variant epitope of Pfs48/45, a Plasmodium falciparum transmissionblocking vaccine candidate. Mol. Biochem. Parasitol. 81: 253– 257.

15. Escalante, A. A.,, and F. J. Ayala. 1994. Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proc. Natl. Acad. Sci. USA 91: 11373– 11377.

16. Escalante, A. A.,, and F. J. Ayala. 1995. Evolutionary origin of Plasmodium and other apicomplexa based on rRNA genes. Proc. Natl. Acad. Sci. USA 92: 5793– 5799.

17. Escalante, A. A.,, E. Barrio,, and F. J. Ayala. 1995. Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein. Mol. Biol. Evol. 12: 616– 626.

18. Escalante, A. A.,, D. E. Freeland,, W. E. Collins,, and A. A. Lal. 1998. The evolution of primate malaria parasites based on the gene encoding cytochrome b from the linear mitochondrial genome. Proc. Natl. Acad. Sci. USA 95: 8124– 8129.

19. Escalante, A. A.,, I. F. Goldman,, P. De Rijk,, R. De Wachter,, W. E. Collins,, S. H. Qari,, and A. A. Lal. 1997. Phylogenetic study of the genus Plasmodium based on the secondary structure-based alignment of the small subunit ribosomal RNA. Mol. Biochem. Parasitol. 90: 317– 321.

20. Feng, X.,, J. M. Carlton,, D. A. Joy,, J. Mu,, T. Furuya,, B. Suh,, Y. Wang,, J. W. Barnwell,, and X.-Z. Su. 2003. Single nucleotide polymorphisms and genome diversity in Plasmodium vivax. Proc. Natl. Acad. Sci. USA 100: 8502– 8507.

21. Figtree, M.,, C. J. Pasay,, R. Slade,, Q. Cheng,, N. Cloonan,, J. Walker,, and A. Saul. 2000. Plasmodium vivax synonymous substitution frequencies, evolution and population structure deduced from diversity in AMA 1 and MSP 1 genes. Mol. Biochem. Parasitol. 108: 53– 66.

22. Gardner, M. J.,, N. Hall,, E. Fung,, O. White,, M. Berriman,, R. W. Hyman,, J. M. Carlton,, A. Pain,, K. E. Nelson,, S. Bowman,, I. T. Paulsen,, K. James,, J. A. Eisen,, K. Rutherford,, S. L. Salzberg,, A. Craig,, S. Kyes,, M. S. Chan,, V. Nene,, S. J. Shallom,, B. Suh,, J. Peterson,, S. Angiuoli,, M. Pertea,, J. Allen,, J. Selengut,, D. Haft,, M. W. Mather,, A. B. Vaidya,, D. M. Martin,, A. H. Fairlamb,, M. J. Fraunholz,, D. S. Roos,, S. A. Ralph,, G. I. McFadden,, L. M. Cummings,, G. M. Subramanian,, C. Mungall,, J. C. Venter,, D. J. Carucci,, S. L. Hoffman,, C. Newbold,, R. W. Davis,, C. M. Fraser,, and B. Barrell. 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498– 511.

23. Gutierrez, A.,, J. Vicini,, M. E. Patarroyo,, L. A. Murillo,, and M. A. Patarroyo. 2000. Plasmodium vivax: polymorphism in the merozoite surface protein 1 gene from wild Colombian isolates. Exp. Parasitol. 95: 215– 219.

24. Hartl, D. L.,, and A. G. Clark. 1997. Principles of Population Genetics, 3rd ed. Sinauer Associates, Sunderland, Mass.

25. Hedges, S. B. 2002. The origin and evolution of model organisms. Nat. Rev. Genet. 3: 838– 849.

26. Hughes, A. L.,, and F. Verra. 2001. Very large longterm effective population size in the virulent human malaria parasite Plasmodium falciparum. Proc. R. Soc. Lond. B Biol. Sci. 268: 1855– 1860.

27. Ingman, M.,, H. Kaessmann,, S. Pääbo,, and U. Glyllensten. 2000. Mitochondrial genome variation and the origin of modern humans. Nature 408: 708– 713.

28. Iwamoto, S.,, J. Li,, N. Sugimoto,, H. Okuda,, and E. Kajii. 1996. Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem. Biophys. Res. Commun. 222: 852– 859.

29. Joy, D. A.,, X. Feng,, J. Mu,, T. Furuya,, K. Chotivanich,, A. U. Krettli,, M. Ho,, A. Wang,, N. J. White,, E. Suh,, P. Beerli,, and X. Su. 2003. Early origin and recent expansion of Plasmodium falciparum. Science 300: 318– 321.

30. Kedzierski, L.,, A. A. Escalante,, R. Isea,, C. G. Black,, J. W. Barnwell,, and R. L. Coppel. 2002. Phylogenetic analysis of the genus Plasmodium based on the gene encoding adenylosuccinate lyase. Infect. Genet. Evol. 1: 297– 301.

31. Kimura, M. 1968. Evolutionary rate at the molecular level. Nature 217: 624– 626.

32. Kissinger, J. C.,, W. E. Collins,, J. Li,, and T. F. Mc-Cutchan. 1998. Plasmodium inui is not closely related to other quartan Plasmodium species. J. Parasitol. 84: 278– 282.

33. Kumar, S.,, and B. S. Hedges. 1998. A molecular timescale for vertebrate evolution. Nature 392: 917– 920.

34. Kurvadina, O. N.,, B. S. Leander,, V. V. Aleshin,, A. P. Myl'Nikov,, P. J. Keeling,, and T. G. Simdyanov. 2002. The phylogeny of colopodellids (Alveolata) using small subunit rRNA gene sequences suggests they are the free-living sister group to apicomplexans. J. Eukaryot. Microbiol. 49: 498– 504.

35. Leander, B. S.,, O. N. Kuvardina,, V. V. Aleshin,, A. P. Mylnikov,, and P. J. Keeling. 2003. Molecular phylogeny and surface morphology of Colpodella edax (Alveolata): insights into the phagotrophic ancestry of apicomplexans. J. Eukaryot. Microbiol. 50: 334– 340.

36. Leclerc, M. C.,, P. Durand,, C. Gauthier,, S. Patot,, N. Billotte,, M. Menegon,, C. Severini,, F. J. Ayala,, and F. Renaud. 2004. Meager genetic variability of the human malaria agent Plasmodium vivax. Proc. Natl.Acad. Sci. USA 101: 14455– 14460.

37. Li, J.,, W. E. Collins,, R. A. Wirtz,, D. Rathore,, A. Lal,, and T. F. McCutchan. 2001. Geographic subdivision of the range of the malaria parasite Plasmodium vivax. Emerg. Infect. Dis. 7: 35– 42.

38. Livingstone, F. B. 1958. Anthropological implications of sickle cell gene distribution in West Africa. Am. Anthropol. 60: 533– 562.

39. McCutchan, T. F.,, J. B. Dame,, L. H. Miller,, and J. Barnwell. 1984. Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science 225: 808– 811.

40. McCutchan, T. F.,, J. C. Kissinger,, M. G. Touray,, J. M. Rogers,, J. Li,, M. Sullivan,, E. M. Braga,, A. U. Krettli,, and L. H. Miller. 1996. Comparison of circumsporozoite proteins from avian and mammalian malarias: biological and phylogenetic implications. Proc. Natl. Acad. Sci. USA 93: 11889– 11894.

41. Miller, L. H.,, S. J. Mason,, D. F. Clyde,, and M. H. McGinnis. 1976. The resistance factor to Plasmodium vivax in blacks: the Duffy blood group genotype, FyFy. New Engl. J. Med. 295: 302– 304.

42. Mu, J.,, J. Duan,, K. D. Makova,, D. A. Joy,, C. Q. Huynh,, O. H. Branch,, W. H. Li,, and X. Z. Su. 2002. Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum. Nature 418: 323– 326.

43. Nielsen, K. M.,, J. Kasper,, M. Choi,, T. Bedford,, K. Kristiansen,, D. F. Wirth,, S. K. Volkman,, E. R. Lozovsky,, and D. L. Hartl. 2003. Gene conversion as a source of nucleotide diversity in Plasmodium falciparum. Mol. Biol. Evol. 20: 726– 734.

44. Pace, N. R. 1997. A molecular view of microbial diversity and the biosphere. Science 276: 734– 740.

45. Paul, R. E. L.,, F. Ariey,, and V. Robert. 2003. The evolutionary ecology of Plasmodium. Ecol. Lett. 6: 866– 880.

46. Perkins, S. L.,, and J. J. Schall. 2002. A molecular phylogeny of malaria parasites recovered from cytochrome b gene sequences. J. Parasitol. 88: 972– 978.

47. Philippe, H. 2000. Long branch attraction and protist phylogeny. Protist 151: 307– 316.

48. Qari, S. H.,, Y. P. Shi,, N. J. Pieniazek,, W. E. Collins,, and A. A. Lal. 1996. Phylogenetic relationship among the malaria parasites based on small subunit rRNA gene sequences: monophyletic nature of the human malaria parasite, Plasmodium falciparum. Mol. Phylogenet. Evol. 6: 157– 165.

49. Rasti, N.,, M. Wahlgren,, and Q. Chen. 2004. Molecular aspects of malaria pathogenesis. FEMS Immunol. Med. Microbiol. 41: 9– 26.

50. Remsen, J.,, and P. O'Grady. 2002. Phylogeny of Drosophilinae (Diptera: Drosophilidae), with comments on combined analysis and character support. Mol. Phylogenet. Evol. 24: 249– 264.

51. Rich, S. M.,, and F. J. Ayala. 2000. Population structure and recent evolution of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 97: 6994– 70001.

52. Rich, S. M.,, R. R. Hudson,, and F. J. Ayala. 1997. Plasmodium falciparum antigenic diversity: evidence of clonal population structure. Proc. Natl. Acad. Sci. USA 94: 13040– 13045.

53. Rich, S. M.,, M. C. Licht,, R. R. Hudson,, and F. J. Ayala. 1998. Malaria's Eve: evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 95: 4425– 4430.

54. Rokas, A.,, B. L. Williams,, N. King,, and S. B. Carroll. 2003. Genome-scale approaches to resolving incongruence in molecular phylogenies. Nature 425: 798– 804.

55. Russell, P. F.,, L. S. West,, R. D. Manwell,, and G. M. MacDonald. 1963. Practical Malariology, 2nd ed. Oxford University Press, London, United Kingdom.

56. Saunders, M. A.,, M. F. Hammer,, and M. W. Nachman. 2002. Nucleotide variability at G6pd and the signature of malarial selection in humans. Genetics 162: 1849– 1861.

57. Schug, M. D.,, C. M. Hutter,, M. A. Noor,, and C. F. Aquadro. 1998. Mutation and evolution of microsatellites in Drosophila melanogaster. Genetica 102–103: 359– 356.

58. Siddall, M. E.,, and J. R. Barta. 1992. Phylogeny of Plasmodium species: estimation and inference. J. Parasitol . 78: 567– 568.

59. Su, X.-Z.,, and J. C. Wootton. 2004. Genetic mapping in the human malaria parasite Plasmodium falciparum. Mol. Microbiol. 53: 1573– 1582.

60. Templeton, A. 2002. Out of Africa again and again. Nature 416: 45– 51.

61. Tishkoff, S. A.,, R. Varkonyi,, N. Cahinhinan,, S. Abbes,, G. Argyropoulos,, G. Destro-Bisol,, A. Drousiotou,, B. Dangerfield,, G. Lefranc,, J. Loiselet,, A. Piro,, M. Stoneking,, A. Tagarelli,, G. Tagarelli,, H. Elias,. E. H. Touma,, S. M. Williams,, and A. G. Clark. 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293: 455– 482.

62. Vaidya, A. B.,, M. S. Lashgari,, L. G. Pologe,, and J. Morrisey. 1993. Structural features of Plasmodium cytochrome-b that may underlie susceptibility to 8- aminoquinolines and hydroxynaphthoquinones. Mol. Biochem. Parasitol. 58: 33– 42.

63. Vargas-Serrato, E.,, V. Corredor,, and M. R. Galinski. 2003. Phylogenetic analysis of CSP and MSP- 9 gene sequences demonstrates the close relationship of Plasmodium coatneyi to Plasmodium knowlesi. Infect. Genet. Evol. 3: 67– 73.

64. Volkman, S. K.,, A. E. Barry,, E. J. Lyons,, K. M. Nielsen,, S. M. Thomas,, M. Choi,, S. S. Thakore,, K. P. Day,, D. F. Wirth,, and D. L. Hartl. 2001. Recent origin of Plasmodium falciparum from a single progenitor. Science 293: 482– 484.

65. Waters, A. P.,, D. G. Higgins,, and T. F. McCutchan. 1991. Plasmodium falciparum appears to have arisen as a result of a lateral transfer between avian and human hosts. Proc. Natl. Acad. Sci. USA 88: 3140– 3144.

66. Waters, A. P.,, D. G. Higgins,, and T. F. McCutchan. 1993. Evolutionary relatedness of some primate models of Plasmodium. Mol. Biol. Evol. 10: 914– 923.

67. White, N. J., 2003. Malaria, p. 1205– 1296. In G. C. Cook, and A. Zumla (ed.), Manson's Tropical Diseases, 21st ed. W. B. Saunders, Philadelphia, Pa.

68. Woese, C. R.,, O. Kandler,, and M. L. Wheelis. 1990. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc. Natl. Acad. Sci. USA 87: 4576– 4579.

69. Zilversmit, M.,, P. M. O'Grady,, and R. DeSalle,. 2002. Shallow genomics, phylogenetics, and evolution in the family Drosophilidae, p. 512– 523. In R. Altman,, A. K. Dunker,, L. Hunter,, K.Lauderdale,, and T. Klein, (ed.) Pacific Symposium on Biocomputing. World Scientific Publishing Co. Pte. Ltd., Riveredge, N. J.

70. Zimmerman, P. A.,, I. Woolley,, G. L. Masinde,, S. M. Miller,, D. T. McNamara,, F. Hazlett,, C. S. Mgone,, M. P. Alpers,, B. Genton,, B. A. Boatini,, and J. W. Kazura. 1999. Emergence of FY*A null in a Plasmodium vivax-endemic region of Papua New Guinea. Proc. Natl.Acad. Sci. USA 96: 13973– 13977.