Population structure shapes copy number variation in malaria parasites

Ian H. Cheeseman, Becky Miller, John C. Tan, Asako Tan, Shalini Nair, Standwell C. Nkhoma, Marcos De Donato, Hectorina Rodulfo, Arjen Dondorp, Oralee H. Branch, Lastenia Ruiz Mesia, Paul Newton, Mayfong Mayxay, Alfred Amambua-Ngwa, David J. Conway, François Nosten, Michael T. Ferdig, Tim J C Anderson

Research output: Contribution to journalArticle

27 Scopus citations


If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from ST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen.

Original languageEnglish (US)
Pages (from-to)603-620
Number of pages18
JournalMolecular Biology and Evolution
Issue number3
StatePublished - Mar 1 2016
Externally publishedYes



  • copy number variation
  • parasitology.
  • population genetics

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Cheeseman, I. H., Miller, B., Tan, J. C., Tan, A., Nair, S., Nkhoma, S. C., De Donato, M., Rodulfo, H., Dondorp, A., Branch, O. H., Mesia, L. R., Newton, P., Mayxay, M., Amambua-Ngwa, A., Conway, D. J., Nosten, F., Ferdig, M. T., & Anderson, T. J. C. (2016). Population structure shapes copy number variation in malaria parasites. Molecular Biology and Evolution, 33(3), 603-620. https://doi.org/10.1093/molbev/msv282