Gene and genome evolution in malaria parasites (Plasmodium species)

在过去的五年中，我们已经发现了多种疟原虫感染非洲猿类（黑猩猩和大猩猩）的证据，这些寄生虫与感染人类的物种密切相关。特别是，我们已经发现了狐猴亚属中包括恶性疟原虫（人类恶性疟疾的主要原因）在内的六个物种的证据：其中三个物种只感染黑猩猩，而另外三个物种只感染大猩猩(1)。恶性疟原虫起源于一种感染大猩猩的寄生虫适应了感染人类(1)。另一种常见的人类疟疾寄生虫是间日疟原虫，人们认为中非的人类没有间日疟原虫，因为它们携带一种达菲阴性突变，这种突变赋予了间日疟原虫感染的抵抗力。然而，我们发现间日疟原虫在非洲中部的黑猩猩和大猩猩中广泛存在(2)。我们现在的总体目标是研究这些寄生虫的进化，试图了解是什么决定了它们的宿主特异性，以及它们如何适应感染不同的宿主(3)。我们在这个领域的工作是与Beatrice Hahn教授（宾夕法尼亚大学）长期合作的一部分。哈恩实验室的成员目前正在为各种猿类寄生虫生成多个基因组序列。该项目将涉及对这些不同疟原虫物种的基因和基因组序列进行生物信息学分析，以研究它们的进化。我们希望比较每个物种的多个基因组序列。需要解决的问题包括适应进化的程度，特别是宿主适应的性质。参与寄生虫-宿主相互作用的基因将被专门研究，但基因组进化的各个方面也将被考虑。

Within the last five years, we have discovered evidence of multiple Plasmodium parasites infecting African apes (chimpanzees and gorillas) that are closely related to species infecting humans. In particular, we have found evidence for six species within the Laverania subgenus that includes Plasmodium falciparum, the major cause of malignant malaria in humans: three of these species exclusively infect chimpanzees, while three more exclusively infect gorillas (1).P. falciparum originated when one of the parasite species infecting gorillas adapted to infect humans (1). The other common form of human malaria parasite is Plasmodium vivax, which is thought to be absent from humans in central Africa because they carry a Duffy-negative mutation that confers resistance to P. vivax infection. However, we have found that P. vivax is widespread among chimpanzees and gorillas across central Africa (2). Our general aim is now to investigate the evolution of these parasites, in an attempt to understand what determines their host specificity and how they have adapted to infecting different hosts (3).Our work in this area is part of a long-running collaboration with Professor Beatrice Hahn (University of Pennsylvania). Members of the Hahn laboratory are currently generating multiple genome sequences for various of these ape parasites. This project will involve bioinformatics analyses of gene and genome sequences derived from these various Plasmodium species, to investigate their evolution.We expect to compare multiple genome sequences from each species. Questions to be addressed include the extent of adaptive evolution in general, and the nature of host-adaptation in particular. Genes involved in parasite-host interactions will be specifically investigated, but various aspects of genome evolution will also be considered.