A systematic map of genetic variation in Plasmodium falciparum.

Claire Kidgell, Sarah K. Volkman, Johanna P. Daily, Justin O. Borevitz, David Plouffe, Yingyao Zhou, Jeffrey R. Johnson, Karine G. Le Roch, Ousmane Sarr, Omar Ndir, Soulyemane Mboup, Serge Batalov, Dyann F. Wirth, Elizabeth A. Winzeler

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume2
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Plasmodium falciparum
GTP Cyclohydrolase
Parasites
Genes
Antimalarials
Folic Acid
Pharmaceutical Preparations
Genome
MDR Genes
Folic Acid Antagonists
Immune Evasion
Falciparum Malaria
Gene Amplification
Enzymes
Drug Resistance
Immune System
Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Kidgell, C., Volkman, S. K., Daily, J. P., Borevitz, J. O., Plouffe, D., Zhou, Y., ... Winzeler, E. A. (2006). A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathogens, 2(6). https://doi.org/10.1371/journal.ppat.0020057

A systematic map of genetic variation in Plasmodium falciparum. / Kidgell, Claire; Volkman, Sarah K.; Daily, Johanna P.; Borevitz, Justin O.; Plouffe, David; Zhou, Yingyao; Johnson, Jeffrey R.; Le Roch, Karine G.; Sarr, Ousmane; Ndir, Omar; Mboup, Soulyemane; Batalov, Serge; Wirth, Dyann F.; Winzeler, Elizabeth A.

In: PLoS Pathogens, Vol. 2, No. 6, 06.2006.

Research output: Contribution to journalArticle

Kidgell, C, Volkman, SK, Daily, JP, Borevitz, JO, Plouffe, D, Zhou, Y, Johnson, JR, Le Roch, KG, Sarr, O, Ndir, O, Mboup, S, Batalov, S, Wirth, DF & Winzeler, EA 2006, 'A systematic map of genetic variation in Plasmodium falciparum.', PLoS Pathogens, vol. 2, no. 6. https://doi.org/10.1371/journal.ppat.0020057
Kidgell, Claire ; Volkman, Sarah K. ; Daily, Johanna P. ; Borevitz, Justin O. ; Plouffe, David ; Zhou, Yingyao ; Johnson, Jeffrey R. ; Le Roch, Karine G. ; Sarr, Ousmane ; Ndir, Omar ; Mboup, Soulyemane ; Batalov, Serge ; Wirth, Dyann F. ; Winzeler, Elizabeth A. / A systematic map of genetic variation in Plasmodium falciparum. In: PLoS Pathogens. 2006 ; Vol. 2, No. 6.
@article{052697df967e4a57b8f7ec567d508cd0,
title = "A systematic map of genetic variation in Plasmodium falciparum.",
abstract = "Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.",
author = "Claire Kidgell and Volkman, {Sarah K.} and Daily, {Johanna P.} and Borevitz, {Justin O.} and David Plouffe and Yingyao Zhou and Johnson, {Jeffrey R.} and {Le Roch}, {Karine G.} and Ousmane Sarr and Omar Ndir and Soulyemane Mboup and Serge Batalov and Wirth, {Dyann F.} and Winzeler, {Elizabeth A.}",
year = "2006",
month = "6",
doi = "10.1371/journal.ppat.0020057",
language = "English (US)",
volume = "2",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - A systematic map of genetic variation in Plasmodium falciparum.

AU - Kidgell, Claire

AU - Volkman, Sarah K.

AU - Daily, Johanna P.

AU - Borevitz, Justin O.

AU - Plouffe, David

AU - Zhou, Yingyao

AU - Johnson, Jeffrey R.

AU - Le Roch, Karine G.

AU - Sarr, Ousmane

AU - Ndir, Omar

AU - Mboup, Soulyemane

AU - Batalov, Serge

AU - Wirth, Dyann F.

AU - Winzeler, Elizabeth A.

PY - 2006/6

Y1 - 2006/6

N2 - Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.

AB - Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.

UR - http://www.scopus.com/inward/record.url?scp=33746633966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746633966&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.0020057

DO - 10.1371/journal.ppat.0020057

M3 - Article

C2 - 16789840

AN - SCOPUS:33745726540

VL - 2

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 6

ER -