Concerted evolution reveals co-adapted amino acid substitutions in Na+K+ ATPase of frogs that prey on toxic toads

Gene duplication is an important source of evolutionary innovation, but the functional distinction between duplicates can be opposed by ongoing gene conversion between them. Here we document a tandem duplication of Na+,K+-ATPase subunit α1 (ATP1A1) sharedby frogs in the genus Leptodactylus,a group of species that feeds on toxic toads. One ATP1A1 paralog evolved resistance to toad toxins while the other paralog retained ancestral susceptibility. Frequent non-allelic gene conversion homogenized most of the paralog sequences,yet the two Leptodactylusparalogs are distinguished by 12 amino acid substitutions that were maintained by strong selection that counteracted gene conversion. Protein-engineering experiments show that two substitutions substantially increase toxin resistance, whereas the 10 additional substitutions mitigate deleterious pleiotropic effects on enzyme function. Our results highlight how neofunctionalized gene duplicates can help pinpoint functional substitutions and their...

基因重复是演化创新的重要来源，但重复基因间持续发生的基因转换，可能会抵消二者间的功能分化。本研究记录了一项发生于细趾蟾属（Leptodactylus）蛙类的Na⁺,K⁺-ATP酶α1亚基（ATP1A1）串联重复事件，该属蛙类以有毒蟾蜍为食。两个ATP1A1旁系同源拷贝中，一个演化出了对蟾蜍毒素的抗性，另一个则保留了祖先的敏感性。频繁发生的非等位基因转换使大部分旁系同源序列趋于同质化，但这两个细趾蟾属旁系同源基因仍存在12个氨基酸替换差异；这些替换通过抵消基因转换的强选择作用得以保留。蛋白质工程实验表明，其中两个氨基酸替换可显著提升毒素抗性，而额外的10个替换则可缓解该酶功能上的有害多效性效应。本研究结果揭示了新功能化的重复基因如何帮助精准定位功能相关氨基酸替换及其……