Sui Yunpeng, Peng Shuanghong
Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Independent Researcher, Beijing, China.
Front Cell Dev Biol. 2021 Feb 11;9:618113. doi: 10.3389/fcell.2021.618113. eCollection 2021.
In recent years, more and more evidence has emerged showing that changes in copy number variations (CNVs) correlated with the transcriptional level can be found during evolution, embryonic development, and oncogenesis. However, the underlying mechanisms remain largely unknown. The success of the induced pluripotent stem cell suggests that genome changes could bring about transformations in protein expression and cell status; conversely, genome alterations generated during embryonic development and senescence might also be the result of genome changes. With rapid developments in science and technology, evidence of changes in the genome affected by transcriptional level has gradually been revealed, and a rational and concrete explanation is needed. Given the preference of the HIV-1 genome to insert into transposons of genes with high transcriptional levels, we propose a mechanism based on retrotransposons facilitated by specific pre-mRNA splicing style and homologous recombination (HR) to explain changes in CNVs in the genome. This mechanism is similar to that of the group II intron that originated much earlier. Under this proposed mechanism, CNVs on genome are dynamically and spontaneously extended in a manner that is positively correlated with transcriptional level or contract as the cell divides during evolution, embryonic development, senescence, and oncogenesis, propelling alterations in them. Besides, this mechanism explains several critical puzzles in these processes. From evidence collected to date, it can be deduced that the message contained in genome is not just three-dimensional but will become four-dimensional, carrying more genetic information.
近年来，越来越多的证据表明，在进化、胚胎发育和肿瘤发生过程中，可以发现与转录水平相关的拷贝数变异（CNV）变化。然而，其潜在机制在很大程度上仍不清楚。诱导多能干细胞的成功表明基因组变化可能导致蛋白质表达和细胞状态的转变；反之，胚胎发育和衰老过程中产生的基因组改变也可能是基因组变化的结果。随着科学技术的快速发展，受转录水平影响的基因组变化证据逐渐被揭示，需要一个合理而具体的解释。鉴于HIV-1基因组倾向于插入到高转录水平基因的转座子中，我们提出一种基于特定前体mRNA剪接方式和同源重组（HR）促进的逆转座子机制来解释基因组中CNV的变化。这种机制类似于起源更早的II类内含子。在这一提出的机制下，基因组上的CNV在进化、胚胎发育、衰老和肿瘤发生过程中，随着细胞分裂以与转录水平呈正相关的方式动态自发地扩展或收缩，推动其发生改变。此外，该机制解释了这些过程中的几个关键谜题。从迄今为止收集的证据可以推断，基因组中包含的信息不仅是三维的，而且将变为四维的，携带更多的遗传信息。
