生物谷報(bào)道：科學(xué)家發(fā)現(xiàn)了可能用于指導(dǎo)開發(fā)利什曼病療法的一小群基因,。這項(xiàng)研究發(fā)表在了6月17日出版的《自然·遺傳學(xué)》雜志上,。
利什曼病的病原體是利什曼原蟲，它由白蛉等昆蟲的叮咬傳播,。每年全世界有200萬(wàn)人感染這種疾病,，迄今為止還沒(méi)有疫苗，也幾乎沒(méi)有有效的治療藥物,。
英國(guó)Wellcome基金會(huì)桑格研究所的Christopher Peacock和他的同事比較了三種利什曼原蟲的完整基因組序列,。這三種分別是嬰兒利什曼原蟲（L. infantum）,、巴西利什曼原蟲（L. braziliensis）和碩大利什曼原蟲(L. major)。
這些寄生蟲能導(dǎo)致各種感染——從由嬰兒利什曼原蟲導(dǎo)致的可能威脅生命的全身感染（內(nèi)臟利什曼?。?，到由碩大利什曼原蟲導(dǎo)致的皮膚感染。
這三種寄生蟲的基因組都含有超過(guò)8000個(gè)基因,，但是科學(xué)家發(fā)現(xiàn)它們只有200種基因各不相同,。
Peacock說(shuō)，這表明利什曼病的嚴(yán)重程度只由一少部分基因決定,，而一種利什曼原蟲獨(dú)有的基因很可能是導(dǎo)致相應(yīng)的利什曼病獨(dú)特癥狀的基因。他說(shuō),，把注意力集中在有限的基因上,，將“有希望加速新的利什曼病療法的開發(fā)”。
這組科學(xué)家還發(fā)現(xiàn)了幾個(gè)基因,，它們對(duì)嬰兒利什曼原蟲導(dǎo)致人類發(fā)病的能力有貢獻(xiàn),。Peacock說(shuō)：“這為將來(lái)發(fā)現(xiàn)有效的藥物靶標(biāo)或者可能的候選疫苗的研究提供了基礎(chǔ)。”
這組科學(xué)家尋找了進(jìn)化速度迅速的基因,，因?yàn)檫@些基因最有可能參與擊敗或者抑制宿主免疫系統(tǒng),。Peacock告訴本網(wǎng)站說(shuō)，這些基因可能是研發(fā)疫苗的良好候選者,，它們也可能對(duì)于發(fā)現(xiàn)利什曼原蟲如何躲避免疫系統(tǒng)有幫助,，而且它們還能讓科學(xué)家更有效地預(yù)測(cè)疫苗是否成功。
印度非政府組織社會(huì)藥理學(xué)學(xué)會(huì)的秘書Swapan Jana說(shuō)：“這項(xiàng)研究的發(fā)現(xiàn)令人印象深刻,。”他還說(shuō)：“利什曼病需要疫苗和新的療法,。這項(xiàng)研究對(duì)這兩個(gè)領(lǐng)域都有幫助。它吸引著科學(xué)家去發(fā)現(xiàn)利什曼病的有效疫苗以及新的藥物療法,。”（援引SciDev.Net）
原始出處:
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.
