Start-gain mutations can introduce novel start codons and generate novel coding sequences that may affect the function of genes. In this study, we systematically investigated the novel start codons that were either polymorphic or fixed in the human genomes. 829 polymorphic start-gain SNVs were identified in the human populations, and the novel start codons introduced by these SNVs have significantly higher activity in translation initiation. Some of these start-gain SNVs were reported to be associated with phenotypes and diseases in previous studies. By comparative genomic analysis, we found 26 human-specific start codons that were fixed after the divergence between the human and chimpanzee, and high-level translation initiation activity was observed on them. The negative selection signal was detected in the novel coding sequences introduced by these human-specific start codons, indicating the important function of these novel coding sequences.

起始增益突变可以引入新的起始密码子并产生可能影响基因功能的新编码序列。在这项研究中，我们系统地研究了人类基因组中多态或固定的新起始密码子。在人群中鉴定出 829 个多态性起始增益 SNV，这些 SNV 引入的新起始密码子在翻译起始中具有显着更高的活性。据报道，其中一些起始增益 SNV 与先前研究中的表型和疾病有关。通过比较基因组分析，我们发现了 26 个人类特有的起始密码子，这些密码子在人类和黑猩猩发生分歧后被固定下来，并在它们身上观察到高水平的翻译起始活性。