Frank S A
Department of Ecology and Evolutionary Biology, University of California, Irvine 92697-2525, USA.
Proc Biol Sci. 1999 Jul 7;266(1426):1397-401. doi: 10.1098/rspb.1999.0793.
Trypanosoma brucei infects various domestic and wild mammals in equatorial Africa. The parasite's genome contains several hundred alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitaemia develops as a series of outbreaks, each outbreak dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types and a new outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. I use a mathematical model of parasitaemia and host immunity to show that small variations in the rate at which each type switches to other types can explain the observations. My model shows that randomly chosen switch rates do not provide sufficiently ordered parasitaemias to match the observations. Instead, minor modifications of switch rates by natural selection are required to develop a sequence of ordered parasitaemias.
布氏锥虫感染赤道非洲的各种家养和野生哺乳动物。该寄生虫的基因组包含数百种可变且高度分化的表面抗原，在任何细胞中只有一种表面抗原会表达。个别细胞偶尔会改变其表面抗原的表达，从而使其能够逃避免疫监视。这些转换似乎以部分随机的方式发生，产生了一组多样的抗原变体。尽管存在这种多样性，但寄生虫血症以一系列爆发的形式发展，每次爆发由相对较少的抗原类型主导。宿主特异性免疫最终清除占主导地位的抗原类型，随后新的爆发由显然一直以低频率存在的抗原类型引发。不同抗原类型这种相继占主导地位的模式仍无法解释。我使用一个寄生虫血症和宿主免疫的数学模型表明，每种类型转换为其他类型的速率的微小变化可以解释这些观察结果。我的模型表明，随机选择的转换速率无法提供足够有序的寄生虫血症来与观察结果相匹配。相反，需要通过自然选择对转换速率进行微小修改，以形成一系列有序的寄生虫血症。
