Genome-Wide Stochastic Adaptive DNA Amplification at Direct and Inverted DNA Repeats in the Parasite Leishmania
Genome-Wide Stochastic Adaptive DNA Amplification at Direct and Inverted DNA Repeats in the Parasite Leishmania
复制标题
DOI：
10.1371/journal.pbio.1001868
复制
发表时间：
2014-05-01
期刊：
影响因子：
9.8
通讯作者：
Ouellette, Marc
中科院分区：
文献类型：
--
作者：
Ubeda, Jean-Michel;Raymond, Frederic;Ouellette, Marc
特定基因座的基因放大在所有生命王国中都有描述。在原生动物寄生虫利什曼原虫中，扩增产物通常是在正向或反向重复序列水平上形成的染色体外环形或线形扩增的一部分。生物信息学筛选显示，重复序列广泛分布于利什曼原虫基因组中，重复序列是染色体特有的，在物种之间保守，通常以低拷贝数存在。利用灵敏的聚合酶链式反应分析，我们提供了利什曼原虫基因组在这些重复序列水平上不断重排的证据，这些重复序列为种群中基因组片段的结构性和随机扩增(和缺失)提供了一个功能平台。这个过程是自适应的，因为有利的染色体外圆形或线形元件的拷贝数随着选择压力的增加而增加，并且当选择被移除时是可逆的。我们还分别通过RAD51重组酶依赖和不依赖的机制提供了关于环状和线性扩增形成的机制的见解。因此，利什曼原虫全基因组在重复序列水平上被随机重排，选择特定基因座拷贝数变化的寄生虫亚群作为一种应对环境变化的策略。
Gene amplification of specific loci has been described in all kingdoms of life. In the protozoan parasite Leishmania, the product of amplification is usually part of extrachromosomal circular or linear amplicons that are formed at the level of direct or inverted repeated sequences. A bioinformatics screen revealed that repeated sequences are widely distributed in the Leishmania genome and the repeats are chromosome-specific, conserved among species, and generally present in low copy number. Using sensitive PCR assays, we provide evidence that the Leishmania genome is continuously being rearranged at the level of these repeated sequences, which serve as a functional platform for constitutive and stochastic amplification (and deletion) of genomic segments in the population. This process is adaptive as the copy number of advantageous extrachromosomal circular or linear elements increases upon selective pressure and is reversible when selection is removed. We also provide mechanistic insights on the formation of circular and linear amplicons through RAD51 recombinase-dependent and -independent mechanisms, respectively. The whole genome of Leishmania is thus stochastically rearranged at the level of repeated sequences, and the selection of parasite subpopulations with changes in the copy number of specific loci is used as a strategy to respond to a changing environment.