Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp.

M. Andreína Pacheco, Alamelu P. Elango, Abir A. Rahman, David Fisher, William E. Collins, John W. Barnwell, Ananias A. Escalante

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Evidence for natural selection, positive or negative, on gene encoding antigens may indicate variation or functional constraints that are immunologically relevant. Most malaria surface antigens with high genetic diversity have been reported to be under positive-diversifying selection. However, antigens with limited genetic variation are usually ignored in terms of the role that natural selection may have in generating such patterns. We investigated orthologous genes encoding two merozoite proteins, MSP8 and MSP10, among several mammalian Plasmodium spp. These antigens, together with MSP1, are among the few MSPs that have two epidermal growth factor-like domains (EGF) at the C-terminal. Those EGF are relatively conserved (low levels of genetic polymorphism) and have been proposed to act as ligands during the invasion of RBCs. We use several evolutionary genetic methods to detect patterns consistent with natural selection acting on MSP8 and MSP10 orthologs in the human parasites Plasmodium falciparum and P. vivax, as well as closely related malarial species found in non-human primates (NHPs). Overall, these antigens have low polymorphism in the human parasites in comparison with the orthologs from other Plasmodium spp. We found that the MSP10 gene polymorphism in P. falciparum only harbor non-synonymous substitutions, a pattern consistent with a gene under positive selection. Evidence of purifying selection was found on the polymorphism observed in both orthologs from P. cynomolgi, a non-human primate parasite closely related to P. vivax, but it was not conclusive in the human parasite. Yet, using phylogenetic base approaches, we found evidence for purifying selection on both MSP8 and MSP10 in the lineage leading to P. vivax. Such antigens evolving under strong functional constraints could become valuable vaccine candidates. We discuss how comparative approaches could allow detecting patterns consistent with negative selection even when there is low polymorphism in the extant populations.

Original languageEnglish (US)
Pages (from-to)978-986
Number of pages9
JournalInfection, Genetics and Evolution
Volume12
Issue number5
DOIs
StatePublished - Jul 2012

Fingerprint

Merozoites
merozoites
Plasmodium
surface proteins
antigen
Membrane Proteins
genetic polymorphism
Genetic Selection
antigens
polymorphism
Parasites
Antigens
protein
parasite
natural selection
parasites
epidermal growth factor
Plasmodium falciparum
Epidermal Growth Factor
gene

Keywords

  • Epidermal growth factor-like domains
  • Malaria vaccine antigen
  • MSP-10
  • MSP-8
  • Negative selection
  • Plasmodium

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Microbiology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Pacheco, M. A., Elango, A. P., Rahman, A. A., Fisher, D., Collins, W. E., Barnwell, J. W., & Escalante, A. A. (2012). Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp. Infection, Genetics and Evolution, 12(5), 978-986. https://doi.org/10.1016/j.meegid.2012.02.009

Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp. / Pacheco, M. Andreína; Elango, Alamelu P.; Rahman, Abir A.; Fisher, David; Collins, William E.; Barnwell, John W.; Escalante, Ananias A.

In: Infection, Genetics and Evolution, Vol. 12, No. 5, 07.2012, p. 978-986.

Research output: Contribution to journalArticle

Pacheco, MA, Elango, AP, Rahman, AA, Fisher, D, Collins, WE, Barnwell, JW & Escalante, AA 2012, 'Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp.', Infection, Genetics and Evolution, vol. 12, no. 5, pp. 978-986. https://doi.org/10.1016/j.meegid.2012.02.009
Pacheco, M. Andreína ; Elango, Alamelu P. ; Rahman, Abir A. ; Fisher, David ; Collins, William E. ; Barnwell, John W. ; Escalante, Ananias A. / Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp. In: Infection, Genetics and Evolution. 2012 ; Vol. 12, No. 5. pp. 978-986.
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