Plasmodium Genomics and Genetics: New Insights into Malaria Pathogenesis, Drug Resistance, Epidemiology, and Evolution

Abstract

SUMMARY Protozoan Plasmodium parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmission, drug responses, and pathogenesis. However, knowledge gaps in parasite biology and host-parasite interactions still remain. Parasites resistant to multiple antimalarial drugs have emerged, while advanced clinical trials have shown partial efficacy for one available vaccine. Here we discuss genetic and genomic studies of Plasmodium biology, host-parasite interactions, population structures, mosquito infectivity, antigenic variation, and targets for treatment and immunization. Knowledge from these studies will advance our understanding of malaria pathogenesis, epidemiology, and evolution and will support work to discover and develop new medicines and vaccines.

Host-Malaria Parasite Interactions and Impacts on Mutual Evolution

“…However, rodent malaria parasites may have a lower degree of antigen diversity and undergo significantly less ectopic recombination than P. falciparum, partly due to the lack of components of the translesion (TLS) polymerases that are required for the recombination events that drive diversification of the multicopy gene families (Kirkman and Deitsch, 2020;Siao et al, 2020). Further discussions on functions of the pir genes can be found here (Cunningham et al, 2010;Su et al, 2019). More studies are necessary to better understand the mechanisms of gene expression regulation and the maintenance of genetic diversity of the pir genes.…”

“…The genomes of many malaria parasites infecting humans (P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi), nonhuman primates (P. reichenowi, P. praefalciparum, P. blacklocki, P. adleri, P. billcollinsi, P. gaboni, P. cynomolgi, P. coatneyi, P. inui, and P. fragile), rodents (P. berghei, P. yoelii, P. chabaudi, and P. vinkei) and birds (P. relictum and P. gallinaceum) have been sequenced and analyzed (Shutler et al, 2005;Pain et al, 2008;Otto et al, 2014aOtto et al, ,b, 2018Lauron et al, 2015;Ansari et al, 2016;Auburn et al, 2016;Sundararaman et al, 2016;Pasini et al, 2017;Rutledge et al, 2017;Bohme et al, 2018;Su et al, 2019). Malaria parasites have relatively small haploid genomes, ranging from 20 to 35 megabases (Mb) that contain 14 chromosomes, a circular plastid genome of ∼35 kb, and multiple copies of a 6-kb mitochondrial DNA (Gardner et al, 2002;Otto et al, 2014a,b;Auburn et al, 2016;Pasini et al, 2017;Bohme et al, 2018).…”

“…The homologous genes in different species of malaria parasites are often found in syntenic blocks arranged in different order on the chromosomes (Carlton et al, 2005;Kooij et al, 2005). For more information on Plasmodium genome and genomics associated with parasite development, diseases, diagnosis, epidemiology, and vaccine development please consult (Kirchner et al, 2016;Bourgard et al, 2018;Escalante and Pacheco, 2019;Galinski, 2019;Garrido-Cardenas et al, 2019;Su et al, 2019;Videvall, 2019).…”

Development of Nested PCR-Heteroduplex Mobility Assay for Determination of Genetic Diversity in the Block 2 Region of the Plasmodium falciparum Merozoite Surface Protein 1 Gene

“…The increasing of the immigration of foreign workers from endemic areas into countries can lead to the spread of malaria between regions [2][3][4][5]. In addition, the genetic variation has been reported as a cause of the mechanisms that escape from the immune response of the host, and the increasing resistance to the antimalarial drugs [6][7][8][9] also is a cause of malaria spreading.…”

The Evolution Study Of 6-Cysteine Family Member Protein of Plasmodium sp. As a Potential Drug Candidate Against Malaria Infection

“…The ACT is a combination of antimalaria drug artemisinin group with other antimalaria groups. Artemisinin act as a shortacting drug for rapid parasitemia reduction while the second antimalaria group serves as a longer-acting partner, which eliminates parasite that survives artemisinin [4].…”