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Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia.

Abstract：

:Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P vivax and 80 P falciparum isolates collected between 2009 and 2013. We found that although P falciparum has undergone population fracturing, the coendemic P vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P falciparum, P vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P vivax and P falciparum parasites. Although population substructuring in P falciparum has resulted in clonal outgrowths of resistant parasites, P vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P vivax's resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P vivax and achieve malaria elimination.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Parobek CM,Lin JT,Saunders DL,Barnett EJ,Lon C,Lanteri CA,Balasubramanian S,Brazeau N,DeConti DK,Garba DL,Meshnick SR,Spring MD,Chuor CM,Bailey JA,Juliano JJ

doi

10.1073/pnas.1608828113

subject

Has Abstract

pub_date

2016-12-13 00:00:00

pages

E8096-E8105

issue

eissn

0027-8424

issn

1091-6490

pii

1608828113

journal_volume

113

pub_type

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Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia.