Volkman S K, Barry A E, Lyons E J, Nielsen K M, Thomas S M, Choi M, Thakore S S, Day K P, Wirth D F, Hartl D L
The Harvard-Oxford Malaria Genome Diversity Project, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Science. 2001 Jul 20;293(5529):482-4. doi: 10.1126/science.1059878.
Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts efforts to control disease caused by this parasite. Genetic variation in antigenic, drug resistance, and pathogenesis determinants is abundant, consistent with an ancient origin of P. falciparum, whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent, consistent with a recent origin of the parasite. To resolve this paradox, we analyzed introns and demonstrated that these are deficient in single-nucleotide polymorphisms, as are synonymous sites in coding regions. These data establish the recent origin of P. falciparum and further provide an explanation for the abundant diversity observed in antigen and other selected genes.
恶性疟原虫的遗传变异性是其传播成功的基础,并阻碍了控制由这种寄生虫引起的疾病的努力。抗原、耐药性和发病机制决定因素的遗传变异丰富,这与恶性疟原虫的古老起源一致,而编码序列中沉默(同义)位点的DNA变异几乎不存在,这与该寄生虫的近期起源一致。为了解决这一矛盾,我们分析了内含子,并证明这些内含子缺乏单核苷酸多态性,编码区的同义位点也是如此。这些数据证实了恶性疟原虫的近期起源,并进一步解释了在抗原和其他选定基因中观察到的丰富多样性。