School of Biological Sciences, University of Nebraska, Lincoln, NE, USA.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.
Curr Biol. 2021 Jun 21;31(12):2530-2538.e10. doi: 10.1016/j.cub.2021.03.089. Epub 2021 Apr 21.
Although gene duplication is an important source of evolutionary innovation, the functional divergence of duplicates can be opposed by ongoing gene conversion between them. Here, we report on the evolution of a tandem duplication of Na,K-ATPase subunit α1 (ATP1A1) shared by frogs in the genus Leptodactylus, a group of species that feeds on toxic toads. One ATP1A1 paralog evolved resistance to toad toxins although the other retained ancestral susceptibility. Within species, frequent non-allelic gene conversion homogenized most of the sequence between the two copies but was counteracted by strong selection on 12 amino acid substitutions that distinguish the two paralogs. Protein-engineering experiments show that two of these substitutions substantially increase toxin resistance, whereas the additional 10 mitigate their deleterious effects on ATPase activity. Our results reveal how examination of neo-functionalized gene duplicate evolution can help pinpoint key functional substitutions and interactions with the genetic backgrounds on which they arise.
虽然基因复制是进化创新的一个重要来源，但它们之间持续的基因转换可能会阻碍重复基因的功能分化。在这里，我们报告了由 Leptodactylus 属的青蛙共享的 Na，K-ATPase 亚基 α1（ATP1A1）串联重复的进化，这是一组以毒蟾蜍为食的物种。尽管另一个保留了祖先的敏感性，但一个 ATP1A1 基因的复制发生了对蟾蜍毒素的抗性进化。在物种内部，频繁的非同等位基因基因转换使两个拷贝之间的大部分序列同质化，但 12 个氨基酸取代的强烈选择抵消了这种同质化，这些取代区分了两个基因的复制。蛋白质工程实验表明，其中两个取代大大增加了毒素抗性，而另外 10 个取代减轻了它们对 ATP 酶活性的有害影响。我们的研究结果揭示了如何通过检查新功能化的基因重复进化来帮助确定关键的功能取代及其与遗传背景的相互作用。
