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A switch in time

This month's Genome Watch highlights how genome analysis can provide insights into the adaptation of Plasmodium falciparum and Plasmodium vivax to human hosts.

Credit: Stefano Iantorno

Many human infectious pathogens are of zoonotic origin. In the case of Plasmodium falciparum and Plasmodium vivax, both parasites are closely related to Plasmodium species that infect great apes such as gorillas, chimpanzees and, more distantly, Old World monkeys. Genome analysis of human malaria parasites and parasites from these outgroups enables the identification of genetic differences that have facilitated adaptation to life in a new host. Two recent studies compare the genomes of P. falciparum and P. vivax with malaria parasites of non-human primates and identify genomic loci that have evolved under selective pressure.

P. falciparum falls into a subgenus of ape-infective parasites known as Laverania. Otto et al. sequenced the genome of Plasmodium reichenowi, a malaria parasite of chimpanzees, and provided the first complete genome assembly for a non-human-infective species in this subgenus1. A remarkable degree of synteny was observed between the chromosomes of P. reichenowi and P. falciparum; the two species differed in only 4 of about 5,000 core genes, with another 35 pseudogene differences. This high genomic conservation suggests that only a small number of genetic changes confers host specificity.

P. vivax has traditionally been clustered with malaria species that infect Asian monkeys, although recently a closer relationship with parasites that infect African great apes has been established, suggesting an African origin for this species2. Cornejo et al. compared the genomes of five P. vivax isolates to those of its closest relatives, macaque-infective Plasmodium cynomolgi and Plasmodium knowlesi, and identified a set of 4,658 shared genes between the 3 species3. However, a large number of genes (2,700) were specific only to the five P. vivax isolates included in the study, which suggests that recent gene expansion has taken place within this species.

Cornejo et al. and Otto et al. went on to use the Hudson–Kreitman–Aguade (HKA) and McDonald–Kreitman (MK) tests to identify genes under selection. Both tests compare the ratio of polymorphisms within a population to the fixed differences between different populations. A gene with many polymorphisms may be indicative of balancing selection, whereas many fixed differences are suggestive of directional selection. Genome-wide analysis confirmed that the strongest selective pressures in P. falciparum and P. vivax affect genes expressed during the erythrocyte stage of their life cycle. In both species, genes encoding proteins involved in the initial recognition of the host erythrocyte, such as surface proteins of invasive merozoites, were positively selected. In particular, Otto et al. found that two gene families that are involved in cell invasion, sera3 and msrp3, are present in human-adapted P. falciparum but not in P. reichenowi; this suggests that these genes had a key role in the transition from chimpanzees to human hosts.

In both P. falciparum and P. vixax, the greatest level of within-species variation is found in the subtelomeres, a chromosomal region that includes many gene families that express proteins exported to the cell surface4. Within this region, Cornejo et al. found that DnaJ family proteins, a class of heat-shock proteins that function as chaperones within parasites, were under directional selection. The DnaJ proteins are involved in refolding molecules central to pathogenesis and have experienced an expansion in P. vivax and P. falciparum lineages5. An important subtelomeric gene family in P. falciparum are the highly variable var genes, which encode PfEMP1 proteins that are exported to the cell surface and are central to pathogenesis. Unexpectedly, Otto et al. found that the organization and number of var genes were broadly conserved between P. falciparum and P. reichenowi. By contrast, the subtelomeric gene numbers of rif and stevor families, which mediate host compatibility, were lower in P. falciparum than in P. reichenowi, suggesting that these gene families, have been more evolutionarily dynamic and thus possibly increased pathogen fitness to survive in a new host.

In summary, these two reports highlight the potential of genome analysis to uncover the evolutionary mechanisms that drove host switching. The authors identified several other genes showing strong signals of selection, although their biological function is unknown; further investigation into the role of those genes promises to be a rich avenue for future functional studies.


  1. 1

    Otto, T. D. et al. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts. Nature Commun. 5, (2014).

  2. 2

    Liu, W. et al. African origin of the malaria parasite Plasmodium vivax. Nature Commun. 5, (2014).

  3. 3

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Correspondence to Thomas Crellen or Stefano Iantorno.

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The authors declare no competing financial interests.

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Crellen, T., Iantorno, S. A switch in time. Nat Rev Microbiol 13, 190 (2015).

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