Vydyam Pratap, Roy Nabamita, Bhattacharyya Mrinal Kanti
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Front Mol Biosci. 2023 Aug 1;10:1223682. doi: 10.3389/fmolb.2023.1223682. eCollection 2023.
The human malaria parasite 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 multigene family. Homologous recombination (HR)-mediated genomic rearrangements have been implicated to play a major role in gene diversification. However, the key molecular factors involved in the generation of diversity at loci are less known. Here, we tested the hypothesis that PfRad51 could carry out recombination between genes that are not homologous but homeologous in nature. We employed the whole-genome sequencing (WGS) approach to investigate recombination events among sequences over 100 generations and compared the rate of sequence rearrangement at the 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 sequences, thereby impacting the diversification of the gene repertoire.
人类疟原虫通过抗原变异维持感染的慢性，这是一种协调良好的免疫逃避机制。该寄生虫抗原变异最显著的分子决定因素包括多基因家族的成员。同源重组（HR）介导的基因组重排被认为在基因多样化中起主要作用。然而，参与基因座多样性产生的关键分子因素尚鲜为人知。在此，我们检验了一个假设，即恶性疟原虫Rad51（PfRad51）可以在本质上并非同源而是同祖异源的基因之间进行重组。我们采用全基因组测序（WGS）方法来研究超过100代的序列之间的重组事件，并比较PfRad51功能正常和缺陷的寄生虫株系中基因座处的序列重排速率。本简要报告提供了证据，表明关键重组酶功能的丧失使寄生虫的同源重组效率低下，并导致序列之间的重组事件减少，从而影响var基因库的多样化。
