Sexual reproduction in trypanosomes

锥虫病是一种主要的牲畜疾病，它在历史上通过摧毁耕畜和生产动物而削弱了撒哈拉以南非洲的农业发展。这种由采采蝇传播的疾病继续严重限制非洲许多国家的畜牧业生产，因为这种疾病非常普遍，影响到大多数主要牲畜物种，包括牛、绵羊、山羊、猪、马、驴和骆驼。兽医几乎没有药物可用于预防或治疗，耐药性正在增加和广泛;没有疫苗。气候变化可能会加剧动物锥虫病的问题，该疾病已经影响到温带以及热带和亚热带地区。该疾病是由被称为锥虫的微观单细胞生物引起的，在受影响牲畜的血液中发现了这种生物。我们研究的目标是找出锥虫如何在它们之间交换遗传物质，以及这是否会产生具有新特征的新型寄生虫。基因交换使基因通过细胞间的转移在细胞群中快速传播。这在病原微生物的情况下尤其重要，因为一旦出现耐药性基因，它就可以迅速传播，使以前有效的药物变得无用。因此，具有性周期的微生物可能比无性繁殖的微生物更难控制。在这里，我们将调查家畜病原体布氏锥虫和T。刚果语。这两种锥虫都由采采蝇携带，但有显著差异：布氏杆菌在苍蝇唾液腺中发育，已知布氏杆菌在此处进行有性繁殖，形成新的杂交菌株;刚果果蝇在其叮咬和进食器官--长鼻中发育，在我们最近的工作中，我们已经表明它也在那里进行基因交换，但迄今为止还没有关于细节的信息。在人类中，配子--卵子和精子--是通过一种特殊的细胞分裂形式产生的，这种分裂形式被称为减数分裂。卵子和精子联合收割机形成一个单一的杂交细胞，称为受精卵，然后发育成胚胎。受精卵的基因组由细胞核中的一组母本和父本染色体以及母本线粒体DNA组成。我们将研究锥虫如何产生配子以及配子如何联合收割机结合形成合子。我们已经确定了锥虫减数分裂通过寻找细胞表达减数分裂特异性蛋白标记的荧光，并将遵循这些减数分裂细胞，看看他们如何产生配子。我们已经证明了配子融合在一起并交换细胞质，但还不知道它们如何联合收割机结合它们的DNA。与人类一样，锥虫具有由成对染色体组成的核DNA和线粒体DNA;然而锥虫线粒体DNA被紧密包装到称为动基体的细胞隔室中。我们从杂交后代的分析中得知，核基因组和动质体基因组都遗传自双亲锥虫。我们的初步实验表明，这些方法是可行的，将产生可解释的数据。到项目结束时，我们将阐明锥虫交换遗传物质的过程。从长远来看，这将为控制牲畜锥虫病的战略提供信息，因为我们将了解有害基因在寄生虫种群中传播的局限性，以及出现牲畜以前从未遇到过的新菌株的可能性。

Trypanosomiasis is a major livestock disease that historically crippled the development of agriculture in sub-Saharan Africa by destroying both draught and production animals. This tsetse fly-transmitted disease continues to severely constrain livestock production in many countries in Africa, because it is very widespread and affects most of the major livestock species, including cattle, sheep, goats, pigs, horses, donkeys and camels. Vets have few drugs available for prophylaxis or treatment, and drug resistance is increasing and widespread; there is no vaccine. Climate change is likely to exacerbate the problem of animal trypanosomiasis, which already affects temperate as well as tropical and subtropical regions.The disease is caused by microscopic, single-celled organisms called trypanosomes, which are found in the blood of affected livestock. The goal of our research is to find out how trypanosomes swap their genetic material among themselves and whether this generates novel types of parasite with new features. Genetic exchange enables the rapid spread of genes through a cell population by transfer from cell to cell. This is particularly important in the case of pathogenic microbes, because once a gene for drug resistance has arisen, it can quickly spread, rendering a previously effective drug useless. A microbe with a sexual cycle is therefore potentially more difficult to control than one that reproduces asexually. Here we will investigate sexual reproduction in the livestock pathogens Trypanosoma brucei and T. congolense. Both these trypanosomes are carried by tsetse flies, but with significant differences: T. brucei develops in the fly salivary glands and this is where it is known to undergo sexual reproduction with formation of novel hybrid strains; T. congolense develops in the fly's biting and feeding apparatus, the proboscis, and in our recent work we have shown it also undergoes genetic exchange there, but as yet have no information on the details. In humans, the gametes - egg and sperm - are produced by a special form of cell division called meiosis. Egg and sperm combine to form a single hybrid cell called the zygote, which then develops into the embryo. The genome of the zygote consists of one set of maternal and paternal chromosomes in the cell nucleus, plus maternal mitochondrial DNA. We will investigate how trypanosomes produce gametes and how the gametes combine to form a zygote. We have identified trypanosomes undergoing meiosis by searching for cells expressing meiosis-specific proteins tagged by fluorescence and will follow these meiotic cells to see how they produce gametes. We have shown that the gametes fuse together and exchange cytoplasm, but do not yet understand how they combine their DNA. Like humans, trypanosomes have both nuclear DNA consisting of paired chromosomes and mitochondrial DNA; however trypanosome mitochondrial DNA is tightly packaged into a cellular compartment called the kinetoplast. We know from analysis of hybrid progeny that both the nuclear and kinetoplast genomes are inherited from both parental trypanosomes.Our preliminary experiments show that the approaches are feasible and will yield interpretable data. By the end of the project we will have elucidated the process by which trypanosomes exchange genetic material. In the long term, this will inform strategies to control livestock trypanosomiasis, because we will understand the limitations to spread of harmful genes through the parasite population and the likelihood of new strains arising that have never been encountered previously by livestock.