Dataset Information

Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

ABSTRACT: Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation.We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection.High genetic diversity (? = 2.4 × 10(-4)), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparison of the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drug-resistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1.The sequence variations observed at drug-resistance loci reflect differences in each country's historical use of antimalarial drugs and may be useful in formulating local malaria treatment guidelines.

SUBMITTER: Ocholla H

PROVIDER: S-EPMC4241944 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

Ocholla Harold H Preston Mark D MD Mipando Mwapatsa M Jensen Anja T R AT Campino Susana S MacInnis Bronwyn B Alcock Daniel D Terlouw Anja A Zongo Issaka I Oudraogo Jean-Bosco JB Djimde Abdoulaye A AA Assefa Samuel S Doumbo Ogobara K OK Borrmann Steffen S Nzila Alexis A Marsh Kevin K Fairhurst Rick M RM Nosten Francois F Anderson Tim J C TJ Kwiatkowski Dominic P DP Craig Alister A Clark Taane G TG Montgomery Jacqui J

The Journal of infectious diseases 20140619 12

<h4>Background</h4>Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation.<h4>Methods</h4>We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection.<h4>Results</h4>High genetic diversity (π = 2.4 × 10(-4)), moderately ...[more]

PMID: 24948693

Similar Datasets

Project description:Mechanisms regulating gene expression in malaria parasites are not well understood. Little is known about how this parasite regulates its gene expression during transition from one developmental stage to another and in response to various environmental conditions. Parasites in a diseased host face environments which differ from the static, well adapted in vitro conditions in culture. Parasites thus need to adapt quickly and effectively to these conditions by establishing transcriptional states which is best suited for better survival. With the discovery of natural antisense transcripts (NATs) in this parasite and considering the various proposed mechanisms by which NATs might regulate gene expression, it has been speculated that these might be playing a critical role in gene regulation. We report here the diversity of NATs that exist in this parasite, using isolates taken directly from patients with differing clinical symptoms caused by malaria infection. A total of 797 NATs targeted against annotated loci have been detected using a custom designed strand specific microarray. Out of these, 545 are unique to this study. The majority of NATs were positively correlated with the expression pattern of the sense transcript. Many were found to be differentially regulated in response to disease conditions. Antisense transcripts mapped to a wide variety of biochemical/ metabolic pathways, especially pathways pertaining to the central carbon metabolism and stress related pathways. Our data strongly suggests that a large group of NATs detected here are unannotated transcription units antisense to annotated gene models. The results reveal a previously unknown set of NATs that prevails in this parasite, their differential regulation in disease conditions and mapping to functionally well annotated genes. The results detailed here call for studies to deduce the possible mechanism of action, which would help in understanding the in vivo pathological adaptations of these parasites.

Dataset Information

Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

Publications

Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets