一个由美英等国科学家组成的国际研究小组近日测定了两种致命疟疾寄生虫的基因组序列。这两种疟疾寄生虫分别名为Plasmodium knowlesi和Plasmodium vivax,其中P. knowlesi最近被认为是感染人类的一个主要疟疾病原体,而P. vivax则会致人极度虚弱,甚至死亡。相关论文发表在10月9日的《自然》(Nature)杂志上。
P. knowlesi的自然宿主是kra猴,不过现在已经确定它能够感染人类。有证据表明,东南亚感染P. knowlesi的人普遍地被误诊为感染了相对更加温和的P. malariae,这导致了不恰当的治疗方式。
P. knowlesi是首个被遗传测序的猴子疟疾寄生虫,为与新近完成的P. vivax基因组和其它已测序的疟原虫基因组进行比较提供了新的研究机会。确定疟疾寄生虫之间的相似和不同有助于挑选遗传标靶,以进行疫苗和药物的研发。
此次测序的另一个疟疾寄生虫是P. vivax,它的致死率仅次于臭名昭著的P. falciparum,75%的疟疾感染及90%的疟疾每年300万致死数都是由后者导致的。
P. vivax是非洲以外疟疾的主要原因,流行于亚洲和中、南美洲潮湿的热带区域。P. vivax感染的疟疾会导致多次复发的严重失能性疾病,有时会导致死亡。
P. vivax能在凉爽季节以及P. falciparum不能耐受的更为温和的气候中传播,这使它能够影响到世界上一半的人口。此外,P. vivax对药物的抗性也越来越普遍,阻碍了对临床案例的管理。
与P. knowlesi一样,测定P. vivax的基因组序列将会产生对其独特生物学特性的研究,而这同样有助于确定新药及疫苗开发的遗传标靶。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature,455, 799-803,A. Pain,M. Berriman
The genome of the simian and human malaria parasite Plasmodium knowlesi
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia1, 2. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated3, and it has a close phylogenetic relationship to Plasmodium vivax 4, the second most important species of human malaria parasite (reviewed in ref.4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone5) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome4 and other sequenced Plasmodium genomes6, 7, 8. In contrast to other Plasmodiumgenomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs9, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
Nature,455, 757-763,Jane M. Carlton,Claire M. Fraser-Liggett
Comparative genomics of the neglected human malaria parasite Plasmodium vivax
The human malaria parasite Plasmodium vivax is responsible for 25–40% of the 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of theP. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.