A paradoxical population structure of var DBLα types in Africa.

The var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var with these ups groups have different chr...

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Main Authors: Mun Hua Tan, Kathryn E Tiedje, Qian Feng, Qi Zhan, Mercedes Pascual, Heejung Shim, Yao-Ban Chan, Karen P Day
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-02-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012813
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author Mun Hua Tan
Kathryn E Tiedje
Qian Feng
Qi Zhan
Mercedes Pascual
Heejung Shim
Yao-Ban Chan
Karen P Day
author_facet Mun Hua Tan
Kathryn E Tiedje
Qian Feng
Qi Zhan
Mercedes Pascual
Heejung Shim
Yao-Ban Chan
Karen P Day
author_sort Mun Hua Tan
collection DOAJ
description The var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var with these ups groups have different chromosomal locations, transcriptional directions, and associations with disease severity. Here we explore temporal and spatial diversity of a region of var genes encoding the DBLα domain of PfEMP1 in Africa. By applying a novel ups classification algorithm (cUps) to publicly-available DBLα sequence datasets, we categorised DBLα according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBLα types in a local population in northern Ghana surveyed seven times from 2012 to 2017 found variants with rare-to-moderate-to-extreme frequencies, and the common variants were temporally stable in this local endemic area. Furthermore, we observed that every isolate repertoire, whether mono- or multiclonal, comprised DBLα types occurring with these frequency ranges implying a common genome structure. When comparing African countries of Ghana, Gabon, Malawi, and Uganda, we report that some DBLα types were consistently found at high frequencies in multiple African countries while others were common only at the country level. The implication of these local and pan-Africa population patterns is discussed in terms of advantage to the parasite with regards to within-host adaptation and resilience to malaria control.
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language English
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spelling doaj-art-bcabf7a0a2424fd9be3da43a96bd9f8b2025-02-12T05:30:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-02-01212e101281310.1371/journal.ppat.1012813A paradoxical population structure of var DBLα types in Africa.Mun Hua TanKathryn E TiedjeQian FengQi ZhanMercedes PascualHeejung ShimYao-Ban ChanKaren P DayThe var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var with these ups groups have different chromosomal locations, transcriptional directions, and associations with disease severity. Here we explore temporal and spatial diversity of a region of var genes encoding the DBLα domain of PfEMP1 in Africa. By applying a novel ups classification algorithm (cUps) to publicly-available DBLα sequence datasets, we categorised DBLα according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBLα types in a local population in northern Ghana surveyed seven times from 2012 to 2017 found variants with rare-to-moderate-to-extreme frequencies, and the common variants were temporally stable in this local endemic area. Furthermore, we observed that every isolate repertoire, whether mono- or multiclonal, comprised DBLα types occurring with these frequency ranges implying a common genome structure. When comparing African countries of Ghana, Gabon, Malawi, and Uganda, we report that some DBLα types were consistently found at high frequencies in multiple African countries while others were common only at the country level. The implication of these local and pan-Africa population patterns is discussed in terms of advantage to the parasite with regards to within-host adaptation and resilience to malaria control.https://doi.org/10.1371/journal.ppat.1012813
spellingShingle Mun Hua Tan
Kathryn E Tiedje
Qian Feng
Qi Zhan
Mercedes Pascual
Heejung Shim
Yao-Ban Chan
Karen P Day
A paradoxical population structure of var DBLα types in Africa.
PLoS Pathogens
title A paradoxical population structure of var DBLα types in Africa.
title_full A paradoxical population structure of var DBLα types in Africa.
title_fullStr A paradoxical population structure of var DBLα types in Africa.
title_full_unstemmed A paradoxical population structure of var DBLα types in Africa.
title_short A paradoxical population structure of var DBLα types in Africa.
title_sort paradoxical population structure of var dblα types in africa
url https://doi.org/10.1371/journal.ppat.1012813
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