Biomedical Research Foundation, Academy of Athens, Athens, Greece.
BMC Evol Biol. 2011 Jul 5;11:193. doi: 10.1186/1471-2148-11-193.
Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila.
In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs.
This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.
域或基因融合分析是一种通过比较一个生物体的基因组与其他生物体的基因组来检测基因融合的生物信息学方法。基因融合的发生表明，参与融合的两个原始基因在功能上是相连的，即它们的基因产物要么作为多亚基蛋白复合物的一部分相互作用，要么在代谢途径中相互作用。基因融合分析已被用于鉴定原核生物以及真核模式生物（如酵母和果蝇）中的蛋白质功能联系。
在本研究中，我们将这种方法扩展到包括一些最近测序的原生动物，其中有四个是致病性的，以鉴定引起非洲昏睡病的寄生虫利什曼原虫中的融合相关蛋白。我们还研究了所鉴定的基因融合事件的进化，通过观察融合基因和单个组成基因在主要真核生物和原核生物谱系中的保守性，来确定它们是否可以归因于融合或裂变。我们发现在所检查的原生动物谱系中，基因融合/裂变的发生相对有限。我们的研究结果表明，有两个与利什曼原虫特异性相关的基因裂变，最近已经通过实验证实，其中一个融合涉及到同一代谢途径中的蛋白质，以及两个新的融合蛋白对之间可能的功能联系。
这是首次通过基因融合分析鉴定利什曼原虫中的蛋白质功能联系的研究。我们使用了严格的阈值，只讨论了极有可能是真实的、已经或可以通过实验验证的结果。我们讨论了鉴定这些新的潜在蛋白-蛋白相互作用对开发新的利什曼原虫治疗药物的可能影响。
