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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

Plasmodium life cycle. After a mosquito bite, malaria parasites are deposited into the host’s skin and within minutes are carried via the bloodstream into the liver, where through asexual proliferation within the hepatocytes tens of thousands of merozoites are produced. Following hepatocyte rupture, merozoites are released into the bloodstream where they can invade the host’s red blood cells (RBC), leading to the initiation of the intra-erythrocytic development cycle (IDC). During the IDC (lasting about 48–72 h in human and about 24 h in rodent malaria parasites), Plasmodium parasites multiply asexually through the completion of several morphologically distinct stages within the RBCs. After RBC invasion, malaria parasites develop via the ring and trophozoite stage into schizonts, each containing a species-specific number of merozoites (typically 10–30). Upon schizont rupture, merozoites are released into the bloodstream, where they can invade new RBCs and initiate a new IDC. However, a small fraction of ring-stage parasites sporadically differentiate into male or female gametocytes, which are responsible for initiating transmission back to the mosquito. Through another mosquito blood meal gametocytes are taken up into the mosquito midgut where they are activated and form male (eight per gametocyte) and female (one) gametes. Following fertilization, the zygote undergoes meiosis (and therefore true sexual recombination) and develops into a motile, tetraploid ookinete that traverses the midgut and forms an oocyst. Via another round of asexual proliferation inside the oocyst several thousands of new haploid sporozoites are generated that, upon their release, colonize the mosquito salivary glands, poised to initiate a new infection of another mammalian host
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Fig2: Plasmodium life cycle. After a mosquito bite, malaria parasites are deposited into the host’s skin and within minutes are carried via the bloodstream into the liver, where through asexual proliferation within the hepatocytes tens of thousands of merozoites are produced. Following hepatocyte rupture, merozoites are released into the bloodstream where they can invade the host’s red blood cells (RBC), leading to the initiation of the intra-erythrocytic development cycle (IDC). During the IDC (lasting about 48–72 h in human and about 24 h in rodent malaria parasites), Plasmodium parasites multiply asexually through the completion of several morphologically distinct stages within the RBCs. After RBC invasion, malaria parasites develop via the ring and trophozoite stage into schizonts, each containing a species-specific number of merozoites (typically 10–30). Upon schizont rupture, merozoites are released into the bloodstream, where they can invade new RBCs and initiate a new IDC. However, a small fraction of ring-stage parasites sporadically differentiate into male or female gametocytes, which are responsible for initiating transmission back to the mosquito. Through another mosquito blood meal gametocytes are taken up into the mosquito midgut where they are activated and form male (eight per gametocyte) and female (one) gametes. Following fertilization, the zygote undergoes meiosis (and therefore true sexual recombination) and develops into a motile, tetraploid ookinete that traverses the midgut and forms an oocyst. Via another round of asexual proliferation inside the oocyst several thousands of new haploid sporozoites are generated that, upon their release, colonize the mosquito salivary glands, poised to initiate a new infection of another mammalian host

Mentions: Within their mammalian host and mosquito vector Plasmodium parasites complete a remarkable lifecycle, alternating between asexual and sexual replication (Fig. 2). Throughout the Plasmodium lifecycle, regulation of gene expression is orchestrated by a variety of mechanisms, including epigenetic, transcriptional, post-transcriptional, and translational control of gene expression. Owing to the absence of most canonical eukaryotic transcription factors in the Plasmodium genome [2], epigenetic control has long been recognized to play an important role in gene expression regulation.Fig. 2


Recent advances in malaria genomics and epigenomics
Plasmodium life cycle. After a mosquito bite, malaria parasites are deposited into the host’s skin and within minutes are carried via the bloodstream into the liver, where through asexual proliferation within the hepatocytes tens of thousands of merozoites are produced. Following hepatocyte rupture, merozoites are released into the bloodstream where they can invade the host’s red blood cells (RBC), leading to the initiation of the intra-erythrocytic development cycle (IDC). During the IDC (lasting about 48–72 h in human and about 24 h in rodent malaria parasites), Plasmodium parasites multiply asexually through the completion of several morphologically distinct stages within the RBCs. After RBC invasion, malaria parasites develop via the ring and trophozoite stage into schizonts, each containing a species-specific number of merozoites (typically 10–30). Upon schizont rupture, merozoites are released into the bloodstream, where they can invade new RBCs and initiate a new IDC. However, a small fraction of ring-stage parasites sporadically differentiate into male or female gametocytes, which are responsible for initiating transmission back to the mosquito. Through another mosquito blood meal gametocytes are taken up into the mosquito midgut where they are activated and form male (eight per gametocyte) and female (one) gametes. Following fertilization, the zygote undergoes meiosis (and therefore true sexual recombination) and develops into a motile, tetraploid ookinete that traverses the midgut and forms an oocyst. Via another round of asexual proliferation inside the oocyst several thousands of new haploid sporozoites are generated that, upon their release, colonize the mosquito salivary glands, poised to initiate a new infection of another mammalian host
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5015228&req=5

Fig2: Plasmodium life cycle. After a mosquito bite, malaria parasites are deposited into the host’s skin and within minutes are carried via the bloodstream into the liver, where through asexual proliferation within the hepatocytes tens of thousands of merozoites are produced. Following hepatocyte rupture, merozoites are released into the bloodstream where they can invade the host’s red blood cells (RBC), leading to the initiation of the intra-erythrocytic development cycle (IDC). During the IDC (lasting about 48–72 h in human and about 24 h in rodent malaria parasites), Plasmodium parasites multiply asexually through the completion of several morphologically distinct stages within the RBCs. After RBC invasion, malaria parasites develop via the ring and trophozoite stage into schizonts, each containing a species-specific number of merozoites (typically 10–30). Upon schizont rupture, merozoites are released into the bloodstream, where they can invade new RBCs and initiate a new IDC. However, a small fraction of ring-stage parasites sporadically differentiate into male or female gametocytes, which are responsible for initiating transmission back to the mosquito. Through another mosquito blood meal gametocytes are taken up into the mosquito midgut where they are activated and form male (eight per gametocyte) and female (one) gametes. Following fertilization, the zygote undergoes meiosis (and therefore true sexual recombination) and develops into a motile, tetraploid ookinete that traverses the midgut and forms an oocyst. Via another round of asexual proliferation inside the oocyst several thousands of new haploid sporozoites are generated that, upon their release, colonize the mosquito salivary glands, poised to initiate a new infection of another mammalian host
Mentions: Within their mammalian host and mosquito vector Plasmodium parasites complete a remarkable lifecycle, alternating between asexual and sexual replication (Fig. 2). Throughout the Plasmodium lifecycle, regulation of gene expression is orchestrated by a variety of mechanisms, including epigenetic, transcriptional, post-transcriptional, and translational control of gene expression. Owing to the absence of most canonical eukaryotic transcription factors in the Plasmodium genome [2], epigenetic control has long been recognized to play an important role in gene expression regulation.Fig. 2

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