Keely Scott P, Renauld Hubert, Wakefield Ann E, Cushion Melanie T, Smulian A George, Fosker Nigel, Fraser Audrey, Harris David, Murphy Lee, Price Claire, Quail Michael A, Seeger Kathy, Sharp Sarah, Tindal Carolyn J, Warren Tim, Zuiderwijk Eduard, Barrell Barclay G, Stringer James R, Hall Neil
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Genetics. 2005 Aug;170(4):1589-600. doi: 10.1534/genetics.105.040733. Epub 2005 Jun 18.
In the fungus Pneumocystis carinii, at least three gene families (PRT1, MSR, and MSG) have the potential to generate high-frequency antigenic variation, which is likely to be a strategy by which this parasitic fungus is able to prolong its survival in the rat lung. Members of these gene families are clustered at chromosome termini, a location that fosters recombination, which has been implicated in selective expression of MSG genes. To gain insight into the architecture, evolution, and regulation of these gene clusters, six telomeric segments of the genome were sequenced. Each of the segments began with one or more unique genes, after which were members of different gene families, arranged in a head-to-tail array. The three-gene repeat PRT1-MSR-MSG was common, suggesting that duplications of these repeats have contributed to expansion of all three families. However, members of a gene family in an array were no more similar to one another than to members in other arrays, indicating rapid divergence after duplication. The intergenic spacers were more conserved than the genes and contained sequence motifs also present in subtelomeres, which in other species have been implicated in gene expression and recombination. Long mononucleotide tracts were present in some MSR genes. These unstable sequences can be expected to suffer frequent frameshift mutations, providing P. carinii with another mechanism to generate antigen variation.
在卡氏肺孢子菌中,至少有三个基因家族(PRT1、MSR和MSG)具有产生高频抗原变异的潜力,这可能是这种寄生真菌能够在大鼠肺中延长其存活时间的一种策略。这些基因家族的成员聚集在染色体末端,该位置有利于重组,而重组与MSG基因的选择性表达有关。为了深入了解这些基因簇的结构、进化和调控,对基因组的六个端粒片段进行了测序。每个片段都以一个或多个独特基因开始,之后是不同基因家族的成员,它们按头对尾的排列方式排列。PRT1-MSR-MSG三基因重复很常见,这表明这些重复序列的复制促进了所有三个家族的扩展。然而,一个阵列中基因家族的成员彼此之间的相似性并不比其他阵列中的成员更高,这表明复制后发生了快速分化。基因间隔区比基因更保守,并且包含在亚端粒中也存在的序列基序,在其他物种中,这些基序与基因表达和重组有关。一些MSR基因中存在长的单核苷酸序列。这些不稳定序列预计会频繁发生移码突变,为卡氏肺孢子菌提供了另一种产生抗原变异的机制。