Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Genes (Basel). 2022 Jan 21;13(2):190. doi: 10.3390/genes13020190.
In his influential book "", Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes and ) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago.
在他颇具影响力的著作《》中，大野乾提出移码突变可能在基因重复后导致新的功能，但移码突变通常被认为是有害的，因此在重复进化中的功能创新中很少受到关注。为此，我们对人类、小鼠、斑马鱼和果蝇的基因组进行了全面调查。我们鉴定了 80 个在重复后发生移码突变的重复基因。大多数情况下，移码突变优先靠近 C 末端（55/88），这表明在重复的末端小部分改变阅读框的移码突变可能有助于适应进化（例如，人类基因和），否则这些突变太具破坏性而无法存活。少数情况下（11/80）涉及多个移码突变，表现出阅读框的各种修饰模式。涉及移码突变的重复基因的功能通过序列特征和表达谱得到了证实，这表明移码突变在创造功能新颖性方面具有潜在作用。因此，我们表明基因组中存在相当数量的基因在基因重复后经历了移码突变。我们的结果证明了移码突变在分子进化中的重要性，正如大野乾 50 年前所提出的那样。
