The genomic landscape shaped by selection on transposable elements across 18 mouse strains
The genomic landscape shaped by selection on transposable elements across 18 mouse strains
复制标题
DOI：
10.1186/gb-2012-13-6-r45
复制
发表时间：
2012-01-01
期刊：
影响因子：
12.3
通讯作者：
Ponting, Chris P.
中科院分区：
文献类型：
--
作者：
Nellaker, Christoffer;Keane, Thomas M.;Ponting, Chris P.
背景资料：转座因子（TE）衍生的序列在哺乳动物基因组中占主导地位，可以通过转录和翻译失调来调节基因功能。我们目前对实验室小鼠品系中TE的了解主要限于C57 BL/6 J参考基因组中存在的TE，大多数小鼠TE来自三个不同的类别，即短散布核元件（西内斯），长散布核元件（LINES）和内源性逆转录病毒（ERV）超家族。尽管他们的高患病率，不同的基因组和基因特性控制是否TE优先清除，或保留，遗传漂变或积极选择哺乳动物genomes.Results：使用全基因组测序数据从13个经典的实验室和4个野生衍生的小鼠近交系，我们开发了一个全面的目录103,798多态性TE变种。我们利用这一广泛的数据集来表征Mus谱系中的TE变体，并推断出200多万年来的中性和选择性过程。我们的研究结果表明，大多数的TE变异体是通过男性生殖系，只有少数的TE变异体产生可检测的基因表达的变化。然而，跨菌株的差异表达的基因中有两倍多的TE变种被认定为推定的因果variants as expected.Conclusions：大多数TE变种，导致基因表达的变化似乎被迅速净化选择。我们的研究结果表明，过去的TE插入往往是高度有害的，并有助于根据其可能对基因表达或表型变异的贡献来优先考虑TE变体。
Background: Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined.Results: Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected.Conclusions: Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation.