Mechanism of genetic exchange in American trypanosomes

Mechanism of genetic exchange in American trypanosomes
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DOI:
10.1038/nature01438
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发表时间:
2003-02-27
期刊:
影响因子:
64.8
通讯作者:
Miles, MA
Miles, MA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gaunt, MW;Yeo, M;Miles, MA

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动质体原生动物负责毁灭性的疾病(1)。在美洲,克氏锥虫是南美锥虫病的病原体-一种广泛传播的动物传染给人类的疾病(人畜共患病)-通过接触吸血锥蝽的受感染粪便传播(2)。T. cruzi和利什曼原虫是有争议的(3,4)。在这里,通过产生杂交克隆,我们表明,T。cruzi有现存的基因交换能力。这种机制是不寻常的,与非洲锥虫布氏锥虫的机制不同(5)。将T.转染Cruzi以携带不同的耐药标记(7,8),并在整个生命周期中一起传代。六个双耐药的后代克隆,从生命周期的哺乳动物阶段恢复,显示融合的亲本基因型,等位基因的丢失,同源重组,和单亲遗传的动基体大环DNA。这些实验杂种与自然分离株的基因型有很强的遗传相似性。克鲁兹在这种情况下,通过核杂交产生的非整倍性导致了比孟德尔遗传交换更大的遗传距离的重组。这种机制也与基因组复制平行(9,10)。
The kinetoplastid Protozoa are responsible for devastating diseases(1). In the Americas, Trypanosoma cruzi is the agent of Chagas' disease-a widespread disease transmissible from animals to humans (zoonosis)-which is transmitted by exposure to infected faeces of blood-sucking triatomine bugs(2). The presence of genetic exchange in T. cruzi and in Leishmania is much debated(3,4). Here, by producing hybrid clones, we show that T. cruzi has an extant capacity for genetic exchange. The mechanism is unusual and distinct from that proposed for the African trypanosome, Trypanosoma brucei(5). Two biological clones(6) of T. cruzi were transfected to carry different drug-resistance markers(7,8), and were passaged together through the entire life cycle. Six double-drug-resistant progeny clones, recovered from the mammalian stage of the life cycle, show fusion of parental genotypes, loss of alleles, homologous recombination, and uniparental inheritance of kinetoplast maxicircle DNA. There are strong genetic parallels between these experimental hybrids and the genotypes among natural isolates of T. cruzi. In this instance, aneuploidy through nuclear hybridization results in recombination across far greater genetic distances than mendelian genetic exchange. This mechanism also parallels genome duplication(9,10).