Laboratory of Complex Biological systems and Bioinformatics (CBB), Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Tehran, 1417614411, Iran.
Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Tehran, 1435916471, Iran.
BMC Genom Data. 2022 Jul 27;23(1):59. doi: 10.1186/s12863-022-01075-5.
While the evolutionary divergence of cis-regulatory sequences impacts translation initiation sites (TISs), the implication of tandem repeats (TRs) in TIS selection remains largely elusive. Here, we employed the TIS homology concept to study a possible link between TRs of all core lengths and repeats with TISs.
Human, as reference sequence, and 83 other species were selected, and data was extracted on the entire protein-coding genes (n = 1,611,368) and transcripts (n = 2,730,515) annotated for those species from Ensembl 102. Following TIS identification, two different weighing vectors were employed to assign TIS homology, and the co-occurrence pattern of TISs with the upstream flanking TRs was studied in the selected species. The results were assessed in 10-fold cross-validation.
On average, every TIS was flanked by 1.19 TRs of various categories within its 120 bp upstream sequence, per species. We detected statistically significant enrichment of non-homologous human TISs co-occurring with human-specific TRs. On the contrary, homologous human TISs co-occurred significantly with non-human-specific TRs. 2991 human genes had at least one transcript, TIS of which was flanked by a human-specific TR. Text mining of a number of the identified genes, such as CACNA1A, EIF5AL1, FOXK1, GABRB2, MYH2, SLC6A8, and TTN, yielded predominant expression and functions in the human brain and/or skeletal muscle.
We conclude that TRs ubiquitously flank and contribute to TIS selection at the trans-species level. Future functional analyses, such as a combination of genome editing strategies and in vitro protein synthesis may be employed to further investigate the impact of TRs on TIS selection.
顺式调控序列的进化分歧影响翻译起始位点（TIS），串联重复（TR）在 TIS 选择中的作用仍很大程度上难以捉摸。在这里，我们采用 TIS 同源性概念来研究所有核心长度的 TR 与 TIS 之间可能存在的联系。
选择人类作为参考序列和其他 83 个物种，并从 Ensembl 102 中提取这些物种的整个蛋白质编码基因（n=1611368）和转录本（n=2730515）的数据。在鉴定 TIS 后，使用两个不同的加权向量来分配 TIS 同源性，并在选定的物种中研究 TIS 与上游侧翼 TR 之间的共发生模式。在 10 倍交叉验证中评估结果。
平均而言，每个 TIS 在其 120bp 上游序列中都有 1.19 个来自各种类别的 TR 侧翼，每个物种都有。我们检测到人类特有的 TIS 与人类特异性 TR 共发生存在统计学上显著富集。相反，同源人类 TIS 与非人类特异性 TR 显著共发生。2991 个人类基因至少有一个转录本，其 TIS 被一个人类特异性 TR 所包围。对许多鉴定出的基因（如 CACNA1A、EIF5AL1、FOXK1、GABRB2、MYH2、SLC6A8 和 TTN）进行文本挖掘，发现其主要在人类大脑和/或骨骼肌中表达和发挥功能。
我们得出结论，TR 普遍侧翼并有助于跨物种水平的 TIS 选择。未来的功能分析，如基因组编辑策略和体外蛋白质合成的结合，可以进一步研究 TR 对 TIS 选择的影响。
