Common host variation drives malaria parasite fitness in healthy human red cells

The replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. Deleterious alleles like hemoglobin S are well-known to confer strong resistance to malaria, but the effects of common RBC variation are largely undetermined. Here,...

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Autores principales:	Emily R Ebel, Frans A Kuypers, Carrie Lin, Dmitri A Petrov, Elizabeth S Egan
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	malaria Plasmodium falciparum red blood cells parasite fitness natural variation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/daf0b7ff78b548fd944efedacc14f915
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spelling	oai:doaj.org-article:daf0b7ff78b548fd944efedacc14f9152021-12-01T12:14:27ZCommon host variation drives malaria parasite fitness in healthy human red cells10.7554/eLife.698082050-084Xe69808https://doaj.org/article/daf0b7ff78b548fd944efedacc14f9152021-09-01T00:00:00Zhttps://elifesciences.org/articles/69808https://doaj.org/toc/2050-084XThe replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. Deleterious alleles like hemoglobin S are well-known to confer strong resistance to malaria, but the effects of common RBC variation are largely undetermined. Here, we collected fresh blood samples from 121 healthy donors, most with African ancestry, and performed exome sequencing, detailed RBC phenotyping, and parasite fitness assays. Over one-third of healthy donors unknowingly carried alleles for G6PD deficiency or hemoglobinopathies, which were associated with characteristic RBC phenotypes. Among non-carriers alone, variation in RBC hydration, membrane deformability, and volume was strongly associated with P. falciparum growth rate. Common genetic variants in PIEZO1, SPTA1/SPTB, and several P. falciparum invasion receptors were also associated with parasite growth rate. Interestingly, we observed little or negative evidence for divergent selection on non-pathogenic RBC variation between Africans and Europeans. These findings suggest a model in which globally widespread variation in a moderate number of genes and phenotypes modulates P. falciparum fitness in RBCs.Emily R EbelFrans A KuypersCarrie LinDmitri A PetrovElizabeth S EganeLife Sciences Publications LtdarticlemalariaPlasmodium falciparumred blood cellsparasite fitnessnatural variationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	malaria Plasmodium falciparum red blood cells parasite fitness natural variation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	malaria Plasmodium falciparum red blood cells parasite fitness natural variation Medicine R Science Q Biology (General) QH301-705.5 Emily R Ebel Frans A Kuypers Carrie Lin Dmitri A Petrov Elizabeth S Egan Common host variation drives malaria parasite fitness in healthy human red cells
description	The replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. Deleterious alleles like hemoglobin S are well-known to confer strong resistance to malaria, but the effects of common RBC variation are largely undetermined. Here, we collected fresh blood samples from 121 healthy donors, most with African ancestry, and performed exome sequencing, detailed RBC phenotyping, and parasite fitness assays. Over one-third of healthy donors unknowingly carried alleles for G6PD deficiency or hemoglobinopathies, which were associated with characteristic RBC phenotypes. Among non-carriers alone, variation in RBC hydration, membrane deformability, and volume was strongly associated with P. falciparum growth rate. Common genetic variants in PIEZO1, SPTA1/SPTB, and several P. falciparum invasion receptors were also associated with parasite growth rate. Interestingly, we observed little or negative evidence for divergent selection on non-pathogenic RBC variation between Africans and Europeans. These findings suggest a model in which globally widespread variation in a moderate number of genes and phenotypes modulates P. falciparum fitness in RBCs.
format	article
author	Emily R Ebel Frans A Kuypers Carrie Lin Dmitri A Petrov Elizabeth S Egan
author_facet	Emily R Ebel Frans A Kuypers Carrie Lin Dmitri A Petrov Elizabeth S Egan
author_sort	Emily R Ebel
title	Common host variation drives malaria parasite fitness in healthy human red cells
title_short	Common host variation drives malaria parasite fitness in healthy human red cells
title_full	Common host variation drives malaria parasite fitness in healthy human red cells
title_fullStr	Common host variation drives malaria parasite fitness in healthy human red cells
title_full_unstemmed	Common host variation drives malaria parasite fitness in healthy human red cells
title_sort	common host variation drives malaria parasite fitness in healthy human red cells
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/daf0b7ff78b548fd944efedacc14f915
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Common host variation drives malaria parasite fitness in healthy human red cells

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