Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum

The human malaria parasite Plasmodium falciparum maintains the chronicity of infections through antigenic variation, a well-coordinated immune evasion mechanism. The most prominent molecular determinant of antigenic variation in this parasite includes the members of the var multigene family. Homolog...

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Main Authors: Pratap Vydyam, Nabamita Roy, Mrinal Kanti Bhattacharyya
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1223682/full
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author Pratap Vydyam
Nabamita Roy
Mrinal Kanti Bhattacharyya
author_facet Pratap Vydyam
Nabamita Roy
Mrinal Kanti Bhattacharyya
author_sort Pratap Vydyam
collection DOAJ
description The human malaria parasite Plasmodium falciparum maintains the chronicity of infections through antigenic variation, a well-coordinated immune evasion mechanism. The most prominent molecular determinant of antigenic variation in this parasite includes the members of the var multigene family. Homologous recombination (HR)-mediated genomic rearrangements have been implicated to play a major role in var gene diversification. However, the key molecular factors involved in the generation of diversity at var loci are less known. Here, we tested the hypothesis that PfRad51 could carry out recombination between var genes that are not homologous but homeologous in nature. We employed the whole-genome sequencing (WGS) approach to investigate recombination events among var sequences over 100 generations and compared the rate of sequence rearrangement at the var loci in both PfRad51-proficient and -deficient parasite lines. This brief report provides evidence that the loss of the key recombinase function renders the parasite with inefficient HR and results in fewer recombination events among the var sequences, thereby impacting the diversification of the var gene repertoire.
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spelling doaj.art-a832e158b8f04d958446b4acd4036e722023-08-01T09:42:07ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-08-011010.3389/fmolb.2023.12236821223682Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparumPratap VydyamNabamita RoyMrinal Kanti BhattacharyyaThe human malaria parasite Plasmodium falciparum maintains the chronicity of infections through antigenic variation, a well-coordinated immune evasion mechanism. The most prominent molecular determinant of antigenic variation in this parasite includes the members of the var multigene family. Homologous recombination (HR)-mediated genomic rearrangements have been implicated to play a major role in var gene diversification. However, the key molecular factors involved in the generation of diversity at var loci are less known. Here, we tested the hypothesis that PfRad51 could carry out recombination between var genes that are not homologous but homeologous in nature. We employed the whole-genome sequencing (WGS) approach to investigate recombination events among var sequences over 100 generations and compared the rate of sequence rearrangement at the var loci in both PfRad51-proficient and -deficient parasite lines. This brief report provides evidence that the loss of the key recombinase function renders the parasite with inefficient HR and results in fewer recombination events among the var sequences, thereby impacting the diversification of the var gene repertoire.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1223682/fullmalariaPlasmodium falciparumhomeologous recombinationvar gene rearrangementantigenic variationPfRad51
spellingShingle Pratap Vydyam
Nabamita Roy
Mrinal Kanti Bhattacharyya
Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
Frontiers in Molecular Biosciences
malaria
Plasmodium falciparum
homeologous recombination
var gene rearrangement
antigenic variation
PfRad51
title Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
title_full Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
title_fullStr Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
title_full_unstemmed Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
title_short Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite Plasmodium falciparum
title_sort uncovering the role of rad51 in homologous recombination mediated antigenic diversification in the human malaria parasite plasmodium falciparum
topic malaria
Plasmodium falciparum
homeologous recombination
var gene rearrangement
antigenic variation
PfRad51
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1223682/full
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