Sexual reproduction in trypanosomes

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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.