Gene gain and loss are crucial factors that shape the evolutionary success of diverse organisms. In the past two decades, more attention has been paid to the significance of gene gain through gene duplication or de novo genes. However, gene loss through natural loss-of-function (LoF) mutations, which is prevalent in the genomes of diverse organisms, has been largely ignored. With the development of sequencing techniques, many genomes have been sequenced across diverse species and can be used to study the evolutionary patterns of gene loss. In this review, we summarize recent advances in research on various aspects of LoF mutations, including their identification, evolutionary dynamics in natural populations, and functional effects. In particular, we discuss how LoF mutations can provide insights into the minimum gene set (or the essential gene set) of an organism. Furthermore, we emphasize their potential impact on adaptation. At the genome level, although most LoF mutations are neutral or deleterious, at least some of them are under positive selection and may contribute to biodiversity and adaptation. Overall, we highlight the importance of natural LoF mutations as a robust framework for understanding biological questions in general.

基因的获得和丢失是决定不同生物体进化成功的关键因素。在过去的二十年中，人们越来越关注通过基因复制或从头基因获得基因的重要性。然而，自然功能丧失（LoF）突变导致的基因丢失在不同生物体的基因组中普遍存在，但在很大程度上被忽视了。随着测序技术的发展，许多不同物种的基因组已被测序，可用于研究基因丢失的进化模式。在这篇综述中，我们总结了 LoF 突变各个方面的研究最新进展，包括它们的识别、自然群体中的进化动力学以及功能效应。我们特别讨论了 LoF 突变如何提供对生物体最小基因集（或基本基因集）的见解。此外，我们强调它们对适应的潜在影响。在基因组水平上，虽然大多数 LoF 突变是中性或有害的，但至少其中一些突变处于正选择之下，可能有助于生物多样性和适应。总的来说，我们强调自然 LoF 突变作为理解一般生物学问题的强大框架的重要性。