Positive selection underlies the species‐specific binding of <i>Plasmodium falciparum </i><scp>RH</scp>5 to human basigin

Forni, Diego; Pontremoli, Chiara; Cagliani, Rachele; Clerici, Mario; Sironi, Manuela

doi:10.1111/mec.13354

Cited by 13 publications

(34 citation statements)

References 52 publications

(172 reference statements)

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“…A subsequent population genetic/phylogenetic analysis conducted by Forni et al . [33] found that several of these residues have undergone positive selection in great apes, while a Pf Rh5 residue that stabilizes the interaction with BSG has also been positively selected.…”

Section: Plasmodium Falciparum and The Laverania: A Highly Host Restrmentioning

confidence: 99%

Molecular interactions governing host-specificity of blood stage malaria parasites

Scully

Kanjee

Duraisingh

2017

Current Opinion in Microbiology

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Non-human primates harbor diverse species of malaria parasites, including the progenitors of P. falciparum and P. vivax. Cross-species transmission of some malaria parasites—most notably the macaque parasite, P. knowlesi—continues to this day, compelling the scientific community to ask whether these zoonoses could impede malaria control efforts by acting as a source of recurrent human infection. Host-restriction varies considerably among parasite species and is governed by both ecological and molecular variables. In particular, the efficiency of red blood cell invasion constitutes a prominent barrier to zoonotic emergence. Although proteins expressed upon the erythrocyte surface exhibit considerable diversity both within and among hosts, malaria parasites have adapted to this heterogeneity via the expansion of protein families associated with invasion, offering redundant mechanisms of host cell entry. This molecular toolkit may enable some parasites to circumvent host barriers, potentially yielding host shifts upon subsequent adaptation. Recent studies have begun to elucidate the molecular determinants of host-specificity, as well as the mechanisms that malaria parasites use to overcome these restrictions. We review recent studies concerning host tropism in the context of erythrocyte invasion by focusing on three malaria parasites that span the zoonotic spectrum: P. falciparum, P. knowlesi, and P. vivax.

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Section: Plasmodium Falciparum and The Laverania: A Highly Host Restrmentioning

confidence: 99%

Molecular interactions governing host-specificity of blood stage malaria parasites

Scully

Kanjee

Duraisingh

2017

Current Opinion in Microbiology

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“…Specific amino acid residues in BSG were identified that contribute to recognition of human BSG by PfRh5. Notably, two of these residues, F27 and K191, were identified as targets of positive selection in a study using population genetics and phylogenetics (Forni et al 2015), providing further evidence that this key receptor is under selection pressure both within the human lineage and during NHP evolution.…”

Section: Pfrh5 As a Host Restriction Factormentioning

confidence: 88%

Host Cell Tropism and Adaptation of Blood-Stage Malaria Parasites: Challenges for Malaria Elimination

Lim¹,

Dankwa²,

Paul³

et al. 2017

Cold Spring Harb Perspect Med

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and account for most of the mortality and morbidity associated with malaria in humans. Research and control efforts have focused on infections caused by and , but have neglected other malaria parasite species that infect humans. Additionally, many related malaria parasite species infect nonhuman primates (NHPs), and have the potential for transmission to humans. For malaria elimination, the varied and specific challenges of all of these species will need to be considered. Recent advances in molecular genetics and genomics have increased our knowledge of the prevalence and existing diversity of the human and NHP species. We are beginning to identify the extent of the reservoirs of each parasite species in humans and NHPs, revealing their origins as well as potential for adaptation in humans. Here, we focus on the red blood cell stage of human infection and the host cell tropism of each human species. Determinants of tropism are unique among malaria parasite species, presenting a complex challenge for malaria elimination.

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“…vivax / P . knowlesi (Duffy antigen) were previously shown to have evolved under positive selection in primate phylogenies 66 , 67 . It is thus conceivable that other genes that encode molecules involved in Plasmodium infection or pathogenesis have evolved to avoid or limit the fitness costs imposed on primates by these parasites.…”

Section: Discussionmentioning

confidence: 99%

Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins

Sironi

Forni

Clerici

et al. 2018

Sci Rep

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Plasmodium parasites exerted a strong selective pressure on primate genomes and mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine protective effects against Plasmodium infection/pathogenesis. We thus hypothesized that ECP-encoding genes have evolved in response to Plasmodium-driven selection. We analyzed the evolutionary history of 15 ECP-encoding genes in primates, as well as of their Plasmodium-encoded ligands (KAHRP, MESA and EMP3). Results indicated that EPB42, SLC4A1, and SPTA1 evolved under pervasive positive selection and that episodes of positive selection tended to occur more frequently in primate species that host a larger number of Plasmodium parasites. Conversely, several genes, including ANK1 and SPTB, displayed extensive signatures of purifying selection in primate phylogenies, Homininae lineages, and human populations, suggesting strong functional constraints. Analysis of Plasmodium genes indicated adaptive evolution in MESA and KAHRP; in the latter, different positively selected sites were located in the spectrin-binding domains. Because most of the positively selected sites in alpha-spectrin localized to the domains involved in the interaction with KAHRP, we suggest that the two proteins are engaged in an arms-race scenario. This observation is relevant because KAHRP is essential for the formation of “knobs”, which represent a major virulence determinant for P. falciparum.

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Positive selection underlies the species‐specific binding of Plasmodium falciparum RH5 to human basigin

Cited by 13 publications

References 52 publications

Molecular interactions governing host-specificity of blood stage malaria parasites

Molecular interactions governing host-specificity of blood stage malaria parasites

Host Cell Tropism and Adaptation of Blood-Stage Malaria Parasites: Challenges for Malaria Elimination

Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins

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