最近,全长基因反转录拷贝在犬科动物中很常见。

Recent, full-length gene retrocopies are common in canids.

机构信息

Department of Population Health and Reproduction, University of California, Davis, Davis, California 95616, USA.

Department of Surgical and Radiological Sciences, University of California, Davis, Davis, California 95616, USA.

出版信息

Genome Res. 2022 Aug 25;32(8):1602-1611. doi: 10.1101/gr.276828.122.

Abstract

Gene retrocopies arise from the reverse transcription and insertion into the genome of processed mRNA transcripts. Although many retrocopies have acquired mutations that render them functionally inactive, most mammals retain active LINE-1 sequences capable of producing new retrocopies. New retrocopies, referred to as retro copy number variants (retroCNVs), may not be identified by standard variant calling techniques in high-throughput sequencing data. Although multiple functional retroCNVs have been associated with skeletal dysplasias in dogs, the full landscape of canid retroCNVs has not been characterized. Here, retroCNV discovery was performed on a whole-genome sequencing data set of 293 canids from 76 breeds. We identified retroCNV parent genes via the presence of mRNA-specific 30-mers, and then identified retroCNV insertion sites through discordant read analysis. In total, we resolved insertion sites for 1911 retroCNVs from 1179 parent genes, 1236 of which appeared identical to their parent genes. Dogs had on average 54.1 total retroCNVs and 1.4 private retroCNVs. We found evidence of expression in testes for 12% (14/113) of the retroCNVs identified in six Golden Retrievers, including four chimeric transcripts, and 97 retroCNVs also had significantly elevated across dog breeds, possibly indicating selection. We applied our approach to a subset of human genomes and detected an average of 4.2 retroCNVs per sample, highlighting a 13-fold relative increase of retroCNV frequency in dogs. Particularly in canids, retroCNVs are a largely unexplored source of genetic variation that can contribute to genome plasticity and that should be considered when investigating traits and diseases.

摘要

基因 retrocopies 是由加工 mRNA 转录本的逆转录和插入基因组引起的。尽管许多 retrocopies 已经获得了使其功能失活的突变,但大多数哺乳动物仍保留有活性的 LINE-1 序列,能够产生新的 retrocopies。新的 retrocopies,称为 retro copy number variants (retroCNVs),可能无法通过高通量测序数据中的标准变异调用技术来识别。尽管在犬类中已经发现多个功能 retroCNVs 与骨骼发育不良有关,但犬类 retroCNVs 的全貌尚未得到描述。在这里,对来自 76 个品种的 293 只犬的全基因组测序数据进行了 retroCNV 发现。我们通过存在 mRNA 特异性 30-mers 来鉴定 retroCNV 亲本基因,然后通过不一致的读取分析来鉴定 retroCNV 插入位点。总共,我们从 1179 个亲本基因中确定了 1911 个 retroCNV 的插入位点,其中 1236 个与亲本基因相同。犬类平均有 54.1 个总 retroCNV 和 1.4 个私有 retroCNV。我们在六个金毛猎犬中发现了 12%(14/113)鉴定的 retroCNVs 在睾丸中表达的证据,包括四个嵌合转录本,97 个 retroCNVs 在犬种中也有显著升高,可能表明选择。我们将我们的方法应用于人类基因组的一个子集,每个样本平均检测到 4.2 个 retroCNV,突出了犬类 retroCNV 频率相对增加了 13 倍。特别是在犬科动物中, retroCNVs 是遗传变异的一个尚未充分探索的来源,它可以为基因组的可塑性做出贡献,在研究性状和疾病时应该考虑到这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efad/9435743/d51f0d76fb1c/1602f01.jpg

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