Tandoh Kwesi Z, Amenga-Etego Lucas, Quashie Neils B, Awandare Gordon, Wilson Michael, Duah-Quashie Nancy O
West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
Department of Epidemiology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Evol Bioinform Online. 2021 Mar 3;17:1176934321999640. doi: 10.1177/1176934321999640. eCollection 2021.
Sub-Saharan Africa is courting the risk of artemisinin resistance (ARTr) emerging in malaria parasites. Current molecular surveillance efforts for ARTr have been built on the utility of kelch13 () validated molecular markers. However, whether these molecular markers will serve the purpose of early detection of artemisinin-resistant parasites in Ghana is hinged on a dependent evolution. Here, we tested the hypothesis that the background genome may be present before the ARTr-conferring variant(s) is selected and that signatures of balancing selection on these genomic loci may serve as an early warning signal of ARTr. We analyzed 12 198 single nucleotide polymorphisms (SNPs) in Ghanaian clinical isolates in the Pf3K MalariaGEN dataset that passed a stringent filtering regimen. We identified signatures of balancing selection in 2 genes (phosphatidylinositol 4-kinase and chloroquine resistance transporter) previously reported as background loci for ARTr. These genes showed statistically significant and high positive values for Tajima's D, Fu and Li's F, and Fu and Li's D. This indicates that the biodiversity required to establish a background genome may have been primed in clinical isolates of from Ghana as of 2010. Despite the absence of ARTr in Ghana to date, our finding supports the current use of for molecular surveillance of ARTr in Ghana and highlights the potential utility of monitoring malaria parasite populations for balancing selection in ARTr precursor background genes as early warning molecular signatures for the emergence of ARTr.
撒哈拉以南非洲正面临疟原虫出现青蒿素耐药性（ARTr）的风险。目前针对ARTr的分子监测工作是基于已验证的kelch13分子标记的实用性开展的。然而，这些分子标记能否用于加纳青蒿素耐药寄生虫的早期检测取决于相关的进化情况。在此，我们检验了以下假设：在赋予ARTr的变异被选择之前，背景基因组可能已经存在，并且这些基因组位点上的平衡选择特征可作为ARTr的早期预警信号。我们分析了Pf3K疟疾基因组数据集中加纳临床分离株的12198个单核苷酸多态性（SNP），这些数据经过了严格的筛选程序。我们在先前报道为ARTr背景位点的2个基因（磷脂酰肌醇4激酶和氯喹抗性转运蛋白）中鉴定出平衡选择特征。这些基因的Tajima's D、Fu和Li's F以及Fu和Li's D显示出具有统计学意义的高正值。这表明截至2010年，在来自加纳的临床分离株中，建立背景基因组所需的生物多样性可能已经具备。尽管加纳目前尚无ARTr，但我们的发现支持目前在加纳使用kelch13进行ARTr的分子监测，并强调监测疟原虫群体中ARTr前体背景基因的平衡选择作为ARTr出现的早期预警分子特征的潜在用途。
