Department of Evolutionary and Environmental Biology, University of Haifa, 3498838, Haifa, Israel.
Institute of Evolution, University of Haifa, 3498838, Haifa, Israel.
Theory Biosci. 2023 Jun;142(2):87-105. doi: 10.1007/s12064-023-00387-z. Epub 2023 Mar 11.
Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the nonresistant but otherwise identical 20A[Formula: see text]T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here, we address this finding with the replacement hypothesis, according to which preexisting genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, an evolutionary process under selection can gradually hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A[Formula: see text]G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called interaction-based evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directed mutational responses to specific environmental pressures are possible. Such mutational phenomena need to be further tested by future studies in natural and artificial settings.
最近的研究结果表明，人类抗疟血红蛋白 S 突变是从头产生的，在具有适应性意义的基因和人群中更为频繁，即在血红蛋白亚基β基因中比非抗性但在其他方面相同的血红蛋白亚基δ基因中的 20A[Formula: see text]T 突变更为频繁，在经历了数代强烈疟疾压力的撒哈拉以南非洲人中比没有经历过的北欧人中更为频繁。这一发现对偶然突变的传统观念提出了根本性的挑战。在这里，我们用替代假说来解决这一发现，根据该假说，先前存在的遗传相互作用可以直接且机械地导致简化和取代它们的突变。因此，在选择压力下的进化过程可以逐渐聚焦于对当前进化适应很重要的相互作用，从而产生与这些适应相关的大效应突变。我们使用多种类型的突变，包括基因融合突变、基因复制突变、RNA 编辑位点的 A[Formula: see text]G 突变和转录相关突变，来例证这一假说，并将其置于称为基于相互作用的进化的突变起源的系统水平观点的更广泛背景下。潜在的后果包括突变压力的相似性可能有助于遗传相关物种的平行进化，基因组组织的进化可能是由突变机制驱动的，转座元件的运动也可能被替代解释，以及对特定环境压力的长期定向突变反应是可能的。这种突变现象需要在自然和人工环境中进行未来的研究进一步验证。
