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Recent advances in malaria genomics and epigenomics

View Article: PubMed Central - PubMed

ABSTRACT

Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines.

No MeSH data available.


Related in: MedlinePlus

Major advances in omics-related fields. This figure highlights landmark studies providing key insights into parasite makeup, development, and pathogenesis (yellow boxes) as well as crucial technical advances (blue boxes) since the first Plasmodium genomes were published in 2002 [2, 5, 12, 13, 27, 29, 31, 39, 40, 42, 43, 48–50, 53, 54, 57, 66, 114, 115, 151, 153–178]. AID auxin-inducible degron, ART artemisinin, cKD conditional knockdown, CRISPR clustered regularly interspaced short palindromic repeats, DD destabilization domain, K13 kelch13, Pb P. berghei, Pf P. falciparum, TSS transcription start site, TF transcription factor, ZNF zinc finger nuclease
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Fig1: Major advances in omics-related fields. This figure highlights landmark studies providing key insights into parasite makeup, development, and pathogenesis (yellow boxes) as well as crucial technical advances (blue boxes) since the first Plasmodium genomes were published in 2002 [2, 5, 12, 13, 27, 29, 31, 39, 40, 42, 43, 48–50, 53, 54, 57, 66, 114, 115, 151, 153–178]. AID auxin-inducible degron, ART artemisinin, cKD conditional knockdown, CRISPR clustered regularly interspaced short palindromic repeats, DD destabilization domain, K13 kelch13, Pb P. berghei, Pf P. falciparum, TSS transcription start site, TF transcription factor, ZNF zinc finger nuclease

Mentions: The landmark of the completion of the genome sequence of a laboratory strain of Pf was achieved over a decade ago [2] (Fig. 1). This has since been accompanied, thanks to plummeting costs and advances in next-generation sequencing (NGS) technologies, by the whole-genome sequencing (WGS) of a wide range of species representing all the major clades of the genus, although the genomes of all known human infectious Plasmodium species remain to be sequenced [3]. However, the combination of NGS and WGS has enabled the development of innovative large-scale genomic studies, for example, for genomic epidemiology [4]. Such population genomics, fueled by collaborative consortia (for example, the Malaria Genomic Epidemiology Network (MalariaGEN; http://www.malariagen.net), have allowed the dynamics of global and local population structures to be assessed and adaptive change in parasite genomes to be monitored in response to threats, such as artemisinin (ART). This is especially true for single-nucleotide polymorphisms (SNPs), and while other aspects of genome variation (such as indels and copy number variation) might currently lag behind, the gaps in the database are known and are firmly in the sights of researchers.Fig. 1


Recent advances in malaria genomics and epigenomics
Major advances in omics-related fields. This figure highlights landmark studies providing key insights into parasite makeup, development, and pathogenesis (yellow boxes) as well as crucial technical advances (blue boxes) since the first Plasmodium genomes were published in 2002 [2, 5, 12, 13, 27, 29, 31, 39, 40, 42, 43, 48–50, 53, 54, 57, 66, 114, 115, 151, 153–178]. AID auxin-inducible degron, ART artemisinin, cKD conditional knockdown, CRISPR clustered regularly interspaced short palindromic repeats, DD destabilization domain, K13 kelch13, Pb P. berghei, Pf P. falciparum, TSS transcription start site, TF transcription factor, ZNF zinc finger nuclease
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5015228&req=5

Fig1: Major advances in omics-related fields. This figure highlights landmark studies providing key insights into parasite makeup, development, and pathogenesis (yellow boxes) as well as crucial technical advances (blue boxes) since the first Plasmodium genomes were published in 2002 [2, 5, 12, 13, 27, 29, 31, 39, 40, 42, 43, 48–50, 53, 54, 57, 66, 114, 115, 151, 153–178]. AID auxin-inducible degron, ART artemisinin, cKD conditional knockdown, CRISPR clustered regularly interspaced short palindromic repeats, DD destabilization domain, K13 kelch13, Pb P. berghei, Pf P. falciparum, TSS transcription start site, TF transcription factor, ZNF zinc finger nuclease
Mentions: The landmark of the completion of the genome sequence of a laboratory strain of Pf was achieved over a decade ago [2] (Fig. 1). This has since been accompanied, thanks to plummeting costs and advances in next-generation sequencing (NGS) technologies, by the whole-genome sequencing (WGS) of a wide range of species representing all the major clades of the genus, although the genomes of all known human infectious Plasmodium species remain to be sequenced [3]. However, the combination of NGS and WGS has enabled the development of innovative large-scale genomic studies, for example, for genomic epidemiology [4]. Such population genomics, fueled by collaborative consortia (for example, the Malaria Genomic Epidemiology Network (MalariaGEN; http://www.malariagen.net), have allowed the dynamics of global and local population structures to be assessed and adaptive change in parasite genomes to be monitored in response to threats, such as artemisinin (ART). This is especially true for single-nucleotide polymorphisms (SNPs), and while other aspects of genome variation (such as indels and copy number variation) might currently lag behind, the gaps in the database are known and are firmly in the sights of researchers.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines.

No MeSH data available.


Related in: MedlinePlus