鱼类基因组中的高度活跃转座子 Passer，有望成为一种新的强大的遗传操作工具。

Passer, a highly active transposon from a fish genome, as a potential new robust genetic manipulation tool.

机构信息

College of Animal Science & Technology, Yangzhou University, Yangzhou, Jiangsu, 225009, China.

Division of Medical Biotechnology, Paul Ehrlich Institute, D-63225 Langen, Germany.

出版信息

Nucleic Acids Res. 2023 Feb 28;51(4):1843-1858. doi: 10.1093/nar/gkad005.

DOI:10.1093/nar/gkad005

PMID:36688327

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9976928/

Abstract

The discovery of new, active DNA transposons can expand the range of genetic tools and provide more options for genomic manipulation. In this study, a bioinformatics analysis suggested that Passer (PS) transposons, which are members of the pogo superfamily, show signs of recent and current activity in animals and may be active in some species. Cell-based transposition assays revealed that the native PS transposases from Gasterosteus aculeatus and Danio rerio displayed very high activity in human cells relative to the Sleeping Beauty transposon. A typical overproduction inhibition phenomenon was observed for PS, and transposition capacity was decreased by ∼12% with each kilobase increase in the insertion size. Furthermore, PS exhibited a pronounced integration preference for genes and their transcriptional regulatory regions. We further show that two domesticated human proteins derived from PS transposases have lost their transposition activity. Overall, PS may represent an alternative with a potentially efficient genetic manipulation tool for transgenesis and mutagenesis applications.

摘要

新的、活跃的 DNA 转座子的发现可以扩展遗传工具的范围，并为基因组操作提供更多选择。在这项研究中，生物信息学分析表明，Passer（PS）转座子是 pogo 超家族的成员，在动物中表现出近期和当前活跃的迹象，并且可能在某些物种中活跃。基于细胞的转座酶活性分析显示，来自硬骨鱼 Gasterosteus aculeatus 和斑马鱼 Danio rerio 的天然 PS 转座酶在人类细胞中的活性相对较高，与 Sleeping Beauty 转座子相比。对于 PS 观察到典型的过度产生抑制现象，并且转座能力随着插入大小每增加 1kb 而降低约 12%。此外，PS 表现出对基因及其转录调控区域的明显整合偏好。我们进一步表明，源自 PS 转座酶的两种家养人类蛋白已经失去了它们的转座酶活性。总体而言，PS 可能代表一种替代方法，具有潜在有效的遗传操作工具，可用于转基因和诱变应用。