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白色念珠菌分离株地理分布多样群体中ALS5和ALS6等位基因变异性分析

Analysis of ALS5 and ALS6 allelic variability in a geographically diverse collection of Candida albicans isolates.

作者信息

Zhao Xiaomin, Oh Soon-Hwan, Jajko Robert, Diekema Daniel J, Pfaller Michael A, Pujol Claude, Soll David R, Hoyer Lois L

机构信息

Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.

出版信息

Fungal Genet Biol. 2007 Dec;44(12):1298-309. doi: 10.1016/j.fgb.2007.05.004. Epub 2007 Jun 2.

Abstract

The Candida albicans ALS (agglutinin-like sequence) gene family encodes eight cell-surface glycoproteins, some of which function in adhesion to host surfaces. ALS genes have a central tandem repeat-encoding domain comprised entirely of head-to-tail copies of a conserved 108-bp sequence. The number of copies of the tandemly repeated sequence varies between C. albicans strains and often between alleles within the same strain. Because ALS alleles can encode different-sized proteins that may have different functional characteristics, defining the range of allelic variability is important. Genomic DNA from C. albicans strains representing the major genetic clades was PCR amplified to determine the number of tandemly repeated sequence copies within the ALS5 and ALS6 central domain. ALS5 alleles had 2-10 tandem repeat sequence copies (mean=4.82 copies) while ALS6 alleles had 2-8 copies (mean=4.00 copies). Despite this variability, tandem repeat copy number was stable in C. albicans strains passaged for 3000 generations. Prevalent alleles and allelic distributions varied among the clades for ALS5 and ALS6. Overall, ALS6 exhibited less variability than ALS5. ALS5 deletions can occur naturally in C. albicans via direct repeats flanking the ALS5 locus. Deletion of both ALS5 alleles was associated particularly with clades III and SA. ALS5 exhibited allelic polymorphisms in the coding region 5' of the tandem repeats; some alleles resembled ALS1, suggesting recombination between these contiguous loci. Natural deletion of ALS5 and the sequence variation within its coding region suggest relaxed selective pressure on this locus, and that Als5p function may be dispensable in C. albicans or redundant within the Als family.

摘要

白色念珠菌ALS(凝集素样序列)基因家族编码8种细胞表面糖蛋白,其中一些在黏附于宿主表面时发挥作用。ALS基因有一个中央串联重复编码结构域,完全由一个保守的108bp序列的首尾相连拷贝组成。串联重复序列的拷贝数在白色念珠菌菌株之间存在差异,并且在同一菌株的等位基因之间也常常不同。由于ALS等位基因可以编码不同大小的蛋白质,这些蛋白质可能具有不同的功能特征,因此确定等位基因变异范围很重要。对代表主要遗传分支的白色念珠菌菌株的基因组DNA进行PCR扩增,以确定ALS5和ALS6中央结构域内串联重复序列的拷贝数。ALS5等位基因有2 - 10个串联重复序列拷贝(平均 = 4.82个拷贝),而ALS6等位基因有2 - 8个拷贝(平均 = 4.00个拷贝)。尽管存在这种变异性,但在传代3000代的白色念珠菌菌株中,串联重复拷贝数是稳定的。ALS5和ALS6的优势等位基因和等位基因分布在各分支之间有所不同。总体而言,ALS6的变异性低于ALS5。ALS5缺失可通过ALS5基因座侧翼的直接重复序列在白色念珠菌中自然发生。两个ALS5等位基因的缺失尤其与分支III和SA相关。ALS5在串联重复序列5'端的编码区域表现出等位基因多态性;一些等位基因类似于ALS1,表明这些相邻基因座之间发生了重组。ALS5的自然缺失及其编码区域内的序列变异表明该基因座的选择压力有所放松,并且Als5p功能在白色念珠菌中可能是可有可无的,或者在Als家族中是冗余的。

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