Assefa Samuel, Lim Caeul, Preston Mark D, Duffy Craig W, Nair Mridul B, Adroub Sabir A, Kadir Khamisah A, Goldberg Jonathan M, Neafsey Daniel E, Divis Paul, Clark Taane G, Duraisingh Manoj T, Conway David J, Pain Arnab, Singh Balbir
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT United Kingdom;
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115;
Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):13027-32. doi: 10.1073/pnas.1509534112. Epub 2015 Oct 5.
Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
由人兽共患寄生虫诺氏疟原虫引起的疟疾病例在东南亚各地以及从该地区返回的旅行者中报告得越来越多。为了检测这种寄生虫的选择特征或异常种群结构的证据，我们调查了最近从马来西亚婆罗洲采集的48份临床分离株以及20世纪60年代从马来西亚半岛和菲律宾分离后在实验室恒河猴中维持的5个品系的基因组序列多样性。总体全基因组核苷酸多样性（π = 6.03 × 10(-3)）远高于主要地方性疟原虫物种恶性疟原虫和间日疟原虫在全球样本中的水平。诺氏疟原虫内部呈现出显著的亚结构，由临床分离株的两个主要同域簇和包含实验室分离株的第三个簇组成。两个临床分离株簇之间存在深度分化[全基因组平均固定指数（FST）= 0.21，9293个单核苷酸多态性（SNP）的固定差异FST = 1.0]。这种分化在基因组中表现出明显的异质性，不同染色体的平均FST值范围从0.08到0.34，并且在几条染色体的区域内还有进一步的显著变化。对最大的簇（簇1，38个分离株）的分析表明种群长期增长，等位基因频率分布呈负偏态（全基因组平均Tajima's D = -1.35）。在此背景下，有证据表明对特定基因存在平衡选择，包括环子孢子蛋白（csp）基因，其Tajima's D值最高（1.57），并且单倍型纯合性扫描表明几个基因组区域受到近期正选择。
