Villum Centre for Biodiversity Genomics, Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark.
Present Address: University of Groningen, University Medical Center Groningen, Department of Pediatrics, 9700 RB Groningen, Netherlands.
Gigascience. 2021 Jan 19;10(1). doi: 10.1093/gigascience/giaa161.
During evolutionary history, molecular mechanisms have emerged to cope with deleterious mutations. Frameshift insertions in protein-coding sequences are extremely rare because they disrupt the reading frame. There are a few known examples of their correction through translational frameshifting, a process that enables ribosomes to skip nucleotides during translation to regain proper reading frame. Corrective frameshifting has been proposed to act on the single base pair insertion at position 174 of the mitochondrial NADH dehydrogenase subunit 3 gene (ND3) that has been observed in several turtles and birds. However, the relatively sparse taxonomic representation has hampered our understanding of the evolution of this insertion in vertebrates.
Here, we analyzed 87,707 ND3 sequences from 10,309 vertebrate taxa to reveal the evolutionary history of this insertion and its common genomic characteristics. We confirmed that the insertion only appears in turtles and birds and reconstructed that it evolved independently in both groups with complex patterns of gains and losses. The insertion was observed in almost all bird orders but was absent in all members of the diverse Passeriformes. We found strong conservation in the nucleotides surrounding the insertion in both turtles and birds, which implies that the insertion enforces structural constraints that could be involved in its correction.
Our study demonstrates that frameshifts can be widespread and can be retained for millions of years if they are embedded in a conserved sequence theme.
在进化历史中，出现了分子机制来应对有害突变。蛋白质编码序列中的移码插入非常罕见，因为它们会破坏阅读框。有少数已知的例子表明，它们可以通过翻译移码来纠正，这种过程使核糖体在翻译过程中跳过核苷酸以恢复正确的阅读框。已经提出了校正移码作用于线粒体 NADH 脱氢酶亚基 3 基因（ND3）第 174 位的单个碱基对插入，在几种龟和鸟类中都观察到了这种插入。然而，相对稀疏的分类代表阻碍了我们对这种插入在脊椎动物中的进化的理解。
在这里，我们分析了来自 10309 种脊椎动物类群的 87707 个 ND3 序列，以揭示这种插入的进化历史及其常见的基因组特征。我们证实，这种插入只出现在龟和鸟类中，并重建了它在这两个群体中独立进化，具有复杂的增益和损失模式。这种插入在几乎所有的鸟类目都有观察到，但在多样化的雀形目成员中都没有观察到。我们在龟和鸟类中都发现了插入周围核苷酸的强烈保守性，这意味着插入强制执行的结构约束可能与其校正有关。
我们的研究表明，如果移码嵌入在保守的序列主题中，它们可能会广泛存在并可以保留数百万年。
