Inter-population Differences in Retrogene Loss and Expression in Humans.
Inter-population Differences in Retrogene Loss and Expression in Humans.
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人类逆转损失和人类表达的差异。
DOI：
10.1371/journal.pgen.1005579
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发表时间：
2015-10
期刊：
影响因子：
4.5
通讯作者：
Makałowska I
中科院分区：
文献类型：
--
作者：
Kabza M;Kubiak MR;Danek A;Rosikiewicz W;Deorowicz S;Polański A;Makałowska I
基因逆转录导致个体之间相当大的遗传变异。最近的研究揭示了至少208个逆转录变异（RDV）的存在，这是一类多态性，其中单个基因组中存在或不存在逆转录。这些RDV大多数是最近的回溯复制。在这项研究中，我们使用了1000个基因组计划第1阶段的结果来调查不同人群中祖先（即与其他灵长类动物共享）逆转录丢失的变化。此外，我们使用来自Ilumina BodyMap项目的RNA-Seq数据以及来自Geuvadis Consortium提供的淋巴母细胞系的数据检查了逆转录表达水平。我们还开发了一种新的方法来检测参考人类基因组中缺失的新型逆转录病毒。我们通过实验证实了检测到的逆转录病毒的存在，并确定了它们在17个不同人群的人类基因组中的存在或不存在。总之，我们能够检测到193 RDV，大多数是由于逆转录删除。这些RDV中的大多数以前没有报告过。我们通过实验证实了在某些个体中经历缺失的11个祖先逆转录基因的表达。除一个逆转录基因外，它们的缺失频率非常低。其余10个逆转录副本的表达、保存和低缺失率可能表明了一些功能。除了存在或不存在表达的逆转录，我们还搜索了群体之间逆转录表达水平的差异，发现9个逆转录基因经历统计学上显著的差异表达。许多逆转录基因，长期以来被认为是基因组的“垃圾”，最近被发现是至关重要的。后移在形成物种、种群和个体之间的差异方面起着重要作用。变化可能由新的追溯事件和/或追溯丢失以及追溯表达式的差异引起。来自不同人群的1092个个体的基因组分析和来自50个个体的转录组，揭示了人群之间转录活性古逆转录丢失频率的差异，以及逆转录表达水平的差异。总的来说，这些结果提供了新的见解的基因组事件的种群间变异，这还没有得到评估的基因丢失。
Gene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression. Many retrogenes, long considered to be genomic “junk”, were recently revealed as vitally important. Retroposition plays an important role in shaping differences between species, populations and individuals. Variation may result either from new retroposition events and/or retrocopy loss, as well as from differences in retrocopy expression. Genome analysis of 1092 individuals from various populations and transcriptomes from 50 individuals, revealed differences between populations in the frequency of transcriptionally active ancient retrocopy loss, as well as differences in retrocopy expression levels. Overall, these results provide new insights into the genomic events of inter-population variation, which has not been evaluated much with respect to gene loss.