生物谷报道：科学家发现了可能用于指导开发利什曼病疗法的一小群基因。这项研究发表在了6月17日出版的《自然·遗传学》杂志上。
利什曼病的病原体是利什曼原虫，它由白蛉等昆虫的叮咬传播。每年全世界有200万人感染这种疾病，迄今为止还没有疫苗，也几乎没有有效的治疗药物。
英国Wellcome基金会桑格研究所的Christopher Peacock和他的同事比较了三种利什曼原虫的完整基因组序列。这三种分别是婴儿利什曼原虫（L. infantum）、巴西利什曼原虫（L. braziliensis）和硕大利什曼原虫(L. major)。
这些寄生虫能导致各种感染——从由婴儿利什曼原虫导致的可能威胁生命的全身感染（内脏利什曼病），到由硕大利什曼原虫导致的皮肤感染。
这三种寄生虫的基因组都含有超过8000个基因，但是科学家发现它们只有200种基因各不相同。
Peacock说，这表明利什曼病的严重程度只由一少部分基因决定，而一种利什曼原虫独有的基因很可能是导致相应的利什曼病独特症状的基因。他说，把注意力集中在有限的基因上，将“有希望加速新的利什曼病疗法的开发”。
这组科学家还发现了几个基因，它们对婴儿利什曼原虫导致人类发病的能力有贡献。Peacock说：“这为将来发现有效的药物靶标或者可能的候选疫苗的研究提供了基础。”
这组科学家寻找了进化速度迅速的基因，因为这些基因最有可能参与击败或者抑制宿主免疫系统。Peacock告诉本网站说，这些基因可能是研发疫苗的良好候选者，它们也可能对于发现利什曼原虫如何躲避免疫系统有帮助，而且它们还能让科学家更有效地预测疫苗是否成功。
印度非政府组织社会药理学学会的秘书Swapan Jana说：“这项研究的发现令人印象深刻。”他还说：“利什曼病需要疫苗和新的疗法。这项研究对这两个领域都有帮助。它吸引着科学家去发现利什曼病的有效疫苗以及新的药物疗法。”（援引SciDev.Net）
原始出处:
Nature Genetics
Published online: 17 June 2007 | doi:10.1038/ng2053
Comparative genomic analysis of three Leishmania species that cause diverse human disease
Christopher S Peacock1, Kathy Seeger1, David Harris1, Lee Murphy1, Jeronimo C Ruiz2, Michael A Quail1, Nick Peters1, Ellen Adlem1, Adrian Tivey1, Martin Aslett1, Arnaud Kerhornou1, Alasdair Ivens1, Audrey Fraser1, Marie-Adele Rajandream1, Tim Carver1, Halina Norbertczak1, Tracey Chillingworth1, Zahra Hance1, Kay Jagels1, Sharon Moule1, Doug Ormond1, Simon Rutter1, Rob Squares1, Sally Whitehead1, Ester Rabbinowitsch1, Claire Arrowsmith1, Brian White1, Scott Thurston1, Frédéric Bringaud3, Sandra L Baldauf4, Adam Faulconbridge4, Daniel Jeffares1, Daniel P Depledge4, Samuel O Oyola4, James D Hilley5, Loislene O Brito2, Luiz R O Tosi2, Barclay Barrell1, Angela K Cruz2, Jeremy C Mottram5, Deborah F Smith4 & Matthew Berriman1
Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.
Figure 2 - Conserved pseudogenes in Leishmania species.
Many Leishmania genes present in all three species retain sequence conservation but have frameshifts and/or in-frame stop codons. Some of these pseudogenes have intact syntenic orthologs in other kinetoplastids. (a) Comparison, using the sequence tool ACT, of a region of conserved synteny containing orthologs of the beta-adaptin 4 gene (gray/yellow) and the adjacent syntenic genes (brown) from L. major, L. infantum, L. braziliensis, T. cruzi and T. brucei. Gray bars represent the forward and reverse strands of DNA. The red-pink lines between sequences represent sequence similarity (tBLASTx). Each of the Leishmania orthologs of the beta-adaptin 4 gene (gray) contains several frameshifts and stop codons, whereas the two trypanosome species have uninterrupted intact copies (yellow). Gene prediction of the Leishmania pseudogenes was done by using similarity and codon bias. (b) Alignment of amino acid sequences from the three Leishmania species with their orthologs in T. cruzi, T. brucei and Trypanosoma vivax, showing that there are conserved domains across all species. The N-terminal -adaptin domain (boxed region) shows conservation between all six species, and the most conserved residues correspond to residues that are restricted in higher eukaryotes.
