Culleton, Richard

Hahn, Beatrice H

Plenderleith, Lindsey J

Sharp, Paul M

English

Paul M Sharp

Lindsey J Plenderleith

Richard Culleton

Beatrice H Hahn

Crossref

Edinburgh Research Explorer

     Edinburgh Research Explorer                                      The African origin of plasmodium vivaxCitation for published version:Sharp, PM, Plenderleith, LJ, Culleton, R & Hahn, BH 2022, 'The African origin of plasmodium vivax', FEMSmicrobiology reviews, vol. 46, no. 4, fuac015. https://doi.org/10.1093/femsre/fuac015Digital Object Identifier (DOI):10.1093/femsre/fuac015Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Peer reviewed versionPublished In:FEMS microbiology reviewsGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 24. Sep. 2022 1     LETTER TO THE EDITOR   The African origin of Plasmodium vivax   Paul M. Sharp1,*, Lindsey J. Plenderleith1, Richard Culleton2 and Beatrice H. Hahn3   1Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK, 2Division of Molecular Parasitology, Ehime University, Ehime 791-0295, Japan and 3Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA   * Corresponding author: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK. E-mail: paul.sharp@ed.ac.uk   2  Rougeron and colleagues recently reviewed the origin of the two major human malaria parasites, Plasmodium falciparum and Plasmodium vivax (Rougeron et al. 2021). They supported their arguments with an evolutionary tree intended to depict the relationships among mammal-infecting Plasmodium species.  However, the phylogeny they represented is based on outdated analyses, and some (erroneous) guesswork. More recent analyses of larger datasets have yielded different results, which are key for correctly interpreting the origins of P. vivax.  The phylogeny shown by Rougeron et al. (2021) in Fig. 1, with relevant aspects repeated in Fig. 3, is described as “mostly based on the results of Galen et al. (2018)”. Galen et al. (2018) were interested in the higher order relationships among Plasmodium and other genera of Haemosporidian parasites and used a dataset of 21 proteins conserved across this broad range of species. More recent analyses by several groups have focused on Plasmodium species infecting mammals, using 30 protein sequences encoded by the apicoplast genome (Arisue et al. 2019), or more than 1,000 protein sequences encoded by the nuclear genome (Rutledge et al. 2017; Sharp et al. 2020); these studies have yielded results that differ from the phylogeny shown in Fig. 1 of Rougeron et al. (2021) in important ways.  First, in Fig. 1 P. fragile, from macaques, is shown as the basal lineage of the clade including P. gonderi, P. vivax and various species infecting Southeast Asian primates. This is curious, since the phylogeny in Galen et al. (2018) as well as many analyses by others (e.g., Arisue et al. 2019; Sharp et al. 2020) have consistently identified P. gonderi (from African monkeys) as clearly the basal lineage of this clade. Moreover, all of these phylogenies place P. fragile with P. knowlesi and P. coatneyi, within the radiation of other species infecting Southeast Asian primates.   Second, in Fig. 1 the P. vivax group, i.e., P. vivax together with closely related “P. vivax-like” (from apes) and P. simium (a recent transmission from humans to South American monkeys), is shown as lying within the radiation of species infecting Southeast Asian primates. This relationship was previously inferred from small numbers of  3  mitochondrial sequences (Mu et al. 2005; Hayakawa et al. 2008), but is clearly outdated. More recent analyses place P. vivax basal to the clade of Southeast Asian parasites (Arisue et al. 2019; Sharp et al. 2020).  Finally, in Fig. 1 P. carteri is shown, tentatively, as clustering outside a clade containing the P. vivax group plus P. simiovale, P. fieldi and P. cynomolgi. Again, this is inconsistent with the literature, since all published phylogenies where the position of P. carteri has strong support depict this species as the closest relative of the P. vivax group (Loy et al. 2017, 2018).   These discrepancies have important implications for the origin of P. vivax in humans. In early studies of limited sequence data, P. vivax appeared to emerge from within the radiation of numerous species infecting primates in Southeast Asia, leading to a widespread belief that the human parasite originated via an ancient transmission from monkeys in that part of the world (Escalante et al. 2005; Mu et al. 2005; Hayakawa et al. 2008). However, this did not explain why people across central Africa have an extremely high frequency of the Duffy-negative mutation, which largely prevents infection by P. vivax. The discovery in Africa of very closely-related P. vivax-like parasites in apes (Liu et al. 2010; Prugnolle et al. 2013; Liu et al. 2014), and of another closely-related species, P. carteri, were clearly inconsistent with the Asian hypothesis. Instead, these findings indicated that the common ancestor of P. carteri and the P. vivax group existed in Africa. Indeed, given that (i) all five major lineages within the mammalian Plasmodium radiation appear to have originated in Africa (Sharp et al. 2020), (ii) the earliest divergence on the lineage leading to P. vivax involves two parasites (P. gonderi and Plasmodium sp. DAJ-2004) that are only found in African monkeys, and (iii) a later split separates the African P. vivax-related clade (including P. carteri) from the clade of parasite species infecting Southeast Asian primates, the only tenable interpretation is that the ancestor of the parasites infecting primates in Asia migrated out-of-Africa only after the divergence of the ancestor of the P. vivax-related clade. Since P.vivax-like can infect humans (Prugnolle et al. 2013), it is also evident that these parasites most likely circulated among all ape species in sub-Saharan Africa, including humans; then,  4  after the spread of the Duffy-negative mutation in humans across Africa, the only P. vivax remaining in humans resulted from a lineage that had escaped out-of-Africa (Sharp et al. 2020).   Rougeron et al. concluded that the origin of P. vivax “remains unclear”, suggesting that there is still a debate between the out-of-Africa and out-of-Asia scenarios. However, current phylogenetic evidence is inconsistent with the out-of-Asia hypothesis. The other compelling evidence comes from genetic diversity. Daron et al. (2021) found that levels of genetic diversity among human P. vivax strains decline with the distance from Southeast Asia, and Rougeron et al. have taken this finding as support for the out-of-Asia scenario. However, this claim ignores the fact that P. vivax-like strains in African apes exhibit 8 times more genetic diversity than human P. vivax (Gilabert et al. 2018; Loy et al. 2018). Scenarios whereby an ancestor of P. vivax was transmitted from monkeys to humans in Southeast Asia, spread across Asia to reach apes in sub-Saharan Africa, and then underwent a bottleneck in humans are far-fetched (Prugnolle et al. 2013), and fail to explain the origin of P. carteri.  In conclusion, current phylogenetic evidence indicates that the lineage leading to P. vivax never left Africa, until it migrated out-of-Africa recently with humans (Sharp et al. 2020). The phylogenetic relationships presented by Rougeron et al. (2021) are erroneous, and as a consequence they obfuscate the progress made by the field in elucidating the origins of human malaria parasites.           5  REFERENCES Arisue N, Hashimoto T, Kawai S et al. Apicoplast phylogeny reveals the position of Plasmodium vivax basal to the Asian primate malaria parasite clade. Sci Rep 2019;9:7274. Daron J, Boissiere A, Boundenga L et al. Population genomic evidence of Plasmodium vivax Southeast Asian origin. Sci Adv 2021;7:eabc3713. Escalante AA, Cornejo OE, Freeland DE et al. A monkey’s tale: The origin of Plasmodium vivax as a human parasite. Proc Natl Acad Sci 2005;102:1980-5. Galen SC, Borner J, Martinsen ES et al. The polyphyly of Plasmodium: comprehensive analyses of the malaria parasites (order Haemosporida) reveal widespread taxonomic conflict. R Soc Open Sci 2018;5:171780. Gilabert A, Otto TD, Rutledge GG et al. Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution. PLoS Biol 2018;16:e2006035. Hayakawa T, Culleton R, Otani H et al. Big bang in the evolution of extant malaria parasites. Molec Biol Evol 2008;25:2233-9. Liu W, Li Y, Learn GH et al. Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature 2010;467:420-5. Liu W, Li Y, Shaw KS et al. African origin of the malaria parasite Plasmodium vivax. Nat Commun 2014;5:3346. Loy DE, Liu W, Li Y et al. Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Int J Parasitol 2017;47:87-97. Loy DE, Plenderleith LJ, Sundararaman SA et al. Evolutionary history of human Plasmodium vivax revealed by genome-wide analysis of related ape parasites. Proc Natl Acad Sci 2018;115:E8450-9. Mu J, Joy DA, Duan J et al. Host switch leads to emergence of Plasmodium vivax malaria in humans. Molec Biol Evol 2005;22:1686-93.  6  Prugnolle F, Rougeron V, Becquart P et al. Diversity, host switching and evolution of Plasmodium vivax infecting African great apes. Proc Natl Acad Sci 2013;110:8123-8. Rougeron V, Boudenga L, Arnathau C et al. A population genetic perspective on the origin, spread and adaptation of the human malaria agents Plasmodium falciparum and Plasmodium vivax. FEMS Microbiol Rev 2021;fuab047:1-24. Rutledge GG, Bohme U, Sanders M et al. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution. Nature 2017;542:101-4. Sharp PM, Plenderleith LJ, Hahn BH. Ape origins of human malaria. Ann Rev Microbiol 2020;74:39-63.   

The African origin of plasmodium vivax

     Edinburgh Research Explorer                                      The African origin of plasmodium vivaxCitation for published version:Sharp, PM, Plenderleith, LJ, Culleton, R & Hahn, BH 2022, 'The African origin of plasmodium vivax', FEMSmicrobiology reviews, vol. 46, no. 4, fuac015. https://doi.org/10.1093/femsre/fuac015Digital Object Identifier (DOI):10.1093/femsre/fuac015Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Peer reviewed versionPublished In:FEMS microbiology reviewsGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 25. Nov. 2025 1     LETTER TO THE EDITOR   The African origin of Plasmodium vivax   Paul M. Sharp1,*, Lindsey J. Plenderleith1, Richard Culleton2 and Beatrice H. Hahn3   1Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK, 2Division of Molecular Parasitology, Ehime University, Ehime 791-0295, Japan and 3Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA   * Corresponding author: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK. E-mail: paul.sharp@ed.ac.uk   2  Rougeron and colleagues recently reviewed the origin of the two major human malaria parasites, Plasmodium falciparum and Plasmodium vivax (Rougeron et al. 2021). They supported their arguments with an evolutionary tree intended to depict the relationships among mammal-infecting Plasmodium species.  However, the phylogeny they represented is based on outdated analyses, and some (erroneous) guesswork. More recent analyses of larger datasets have yielded different results, which are key for correctly interpreting the origins of P. vivax.  The phylogeny shown by Rougeron et al. (2021) in Fig. 1, with relevant aspects repeated in Fig. 3, is described as “mostly based on the results of Galen et al. (2018)”. Galen et al. (2018) were interested in the higher order relationships among Plasmodium and other genera of Haemosporidian parasites and used a dataset of 21 proteins conserved across this broad range of species. More recent analyses by several groups have focused on Plasmodium species infecting mammals, using 30 protein sequences encoded by the apicoplast genome (Arisue et al. 2019), or more than 1,000 protein sequences encoded by the nuclear genome (Rutledge et al. 2017; Sharp et al. 2020); these studies have yielded results that differ from the phylogeny shown in Fig. 1 of Rougeron et al. (2021) in important ways.  First, in Fig. 1 P. fragile, from macaques, is shown as the basal lineage of the clade including P. gonderi, P. vivax and various species infecting Southeast Asian primates. This is curious, since the phylogeny in Galen et al. (2018) as well as many analyses by others (e.g., Arisue et al. 2019; Sharp et al. 2020) have consistently identified P. gonderi (from African monkeys) as clearly the basal lineage of this clade. Moreover, all of these phylogenies place P. fragile with P. knowlesi and P. coatneyi, within the radiation of other species infecting Southeast Asian primates.   Second, in Fig. 1 the P. vivax group, i.e., P. vivax together with closely related “P. vivax-like” (from apes) and P. simium (a recent transmission from humans to South American monkeys), is shown as lying within the radiation of species infecting Southeast Asian primates. This relationship was previously inferred from small numbers of  3  mitochondrial sequences (Mu et al. 2005; Hayakawa et al. 2008), but is clearly outdated. More recent analyses place P. vivax basal to the clade of Southeast Asian parasites (Arisue et al. 2019; Sharp et al. 2020).  Finally, in Fig. 1 P. carteri is shown, tentatively, as clustering outside a clade containing the P. vivax group plus P. simiovale, P. fieldi and P. cynomolgi. Again, this is inconsistent with the literature, since all published phylogenies where the position of P. carteri has strong support depict this species as the closest relative of the P. vivax group (Loy et al. 2017, 2018).   These discrepancies have important implications for the origin of P. vivax in humans. In early studies of limited sequence data, P. vivax appeared to emerge from within the radiation of numerous species infecting primates in Southeast Asia, leading to a widespread belief that the human parasite originated via an ancient transmission from monkeys in that part of the world (Escalante et al. 2005; Mu et al. 2005; Hayakawa et al. 2008). However, this did not explain why people across central Africa have an extremely high frequency of the Duffy-negative mutation, which largely prevents infection by P. vivax. The discovery in Africa of very closely-related P. vivax-like parasites in apes (Liu et al. 2010; Prugnolle et al. 2013; Liu et al. 2014), and of another closely-related species, P. carteri, were clearly inconsistent with the Asian hypothesis. Instead, these findings indicated that the common ancestor of P. carteri and the P. vivax group existed in Africa. Indeed, given that (i) all five major lineages within the mammalian Plasmodium radiation appear to have originated in Africa (Sharp et al. 2020), (ii) the earliest divergence on the lineage leading to P. vivax involves two parasites (P. gonderi and Plasmodium sp. DAJ-2004) that are only found in African monkeys, and (iii) a later split separates the African P. vivax-related clade (including P. carteri) from the clade of parasite species infecting Southeast Asian primates, the only tenable interpretation is that the ancestor of the parasites infecting primates in Asia migrated out-of-Africa only after the divergence of the ancestor of the P. vivax-related clade. Since P.vivax-like can infect humans (Prugnolle et al. 2013), it is also evident that these parasites most likely circulated among all ape species in sub-Saharan Africa, including humans; then,  4  after the spread of the Duffy-negative mutation in humans across Africa, the only P. vivax remaining in humans resulted from a lineage that had escaped out-of-Africa (Sharp et al. 2020).   Rougeron et al. concluded that the origin of P. vivax “remains unclear”, suggesting that there is still a debate between the out-of-Africa and out-of-Asia scenarios. However, current phylogenetic evidence is inconsistent with the out-of-Asia hypothesis. The other compelling evidence comes from genetic diversity. Daron et al. (2021) found that levels of genetic diversity among human P. vivax strains decline with the distance from Southeast Asia, and Rougeron et al. have taken this finding as support for the out-of-Asia scenario. However, this claim ignores the fact that P. vivax-like strains in African apes exhibit 8 times more genetic diversity than human P. vivax (Gilabert et al. 2018; Loy et al. 2018). Scenarios whereby an ancestor of P. vivax was transmitted from monkeys to humans in Southeast Asia, spread across Asia to reach apes in sub-Saharan Africa, and then underwent a bottleneck in humans are far-fetched (Prugnolle et al. 2013), and fail to explain the origin of P. carteri.  In conclusion, current phylogenetic evidence indicates that the lineage leading to P. vivax never left Africa, until it migrated out-of-Africa recently with humans (Sharp et al. 2020). The phylogenetic relationships presented by Rougeron et al. (2021) are erroneous, and as a consequence they obfuscate the progress made by the field in elucidating the origins of human malaria parasites.           5  REFERENCES Arisue N, Hashimoto T, Kawai S et al. Apicoplast phylogeny reveals the position of Plasmodium vivax basal to the Asian primate malaria parasite clade. Sci Rep 2019;9:7274. Daron J, Boissiere A, Boundenga L et al. Population genomic evidence of Plasmodium vivax Southeast Asian origin. Sci Adv 2021;7:eabc3713. Escalante AA, Cornejo OE, Freeland DE et al. A monkey’s tale: The origin of Plasmodium vivax as a human parasite. Proc Natl Acad Sci 2005;102:1980-5. Galen SC, Borner J, Martinsen ES et al. The polyphyly of Plasmodium: comprehensive analyses of the malaria parasites (order Haemosporida) reveal widespread taxonomic conflict. R Soc Open Sci 2018;5:171780. Gilabert A, Otto TD, Rutledge GG et al. Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution. PLoS Biol 2018;16:e2006035. Hayakawa T, Culleton R, Otani H et al. Big bang in the evolution of extant malaria parasites. Molec Biol Evol 2008;25:2233-9. Liu W, Li Y, Learn GH et al. Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature 2010;467:420-5. Liu W, Li Y, Shaw KS et al. African origin of the malaria parasite Plasmodium vivax. Nat Commun 2014;5:3346. Loy DE, Liu W, Li Y et al. Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Int J Parasitol 2017;47:87-97. Loy DE, Plenderleith LJ, Sundararaman SA et al. Evolutionary history of human Plasmodium vivax revealed by genome-wide analysis of related ape parasites. Proc Natl Acad Sci 2018;115:E8450-9. Mu J, Joy DA, Duan J et al. Host switch leads to emergence of Plasmodium vivax malaria in humans. Molec Biol Evol 2005;22:1686-93.  6  Prugnolle F, Rougeron V, Becquart P et al. Diversity, host switching and evolution of Plasmodium vivax infecting African great apes. Proc Natl Acad Sci 2013;110:8123-8. Rougeron V, Boudenga L, Arnathau C et al. A population genetic perspective on the origin, spread and adaptation of the human malaria agents Plasmodium falciparum and Plasmodium vivax. FEMS Microbiol Rev 2021;fuab047:1-24. Rutledge GG, Bohme U, Sanders M et al. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution. Nature 2017;542:101-4. Sharp PM, Plenderleith LJ, Hahn BH. Ape origins of human malaria. Ann Rev Microbiol 2020;74:39-63.   

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The African origin of plasmodium vivax

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