Several previous studies by our group suggest that positive selection can drive certain, not all, genes to be retained in the lagging strand orientation. This is likely the result of multiple factors including accelerated evolution through conflicts between replication and transcription. Liu and Zhang challenge this view, and claim that our method for detecting gene inversions is flawed. Here, we provide empirical evidence that their criticisms are largely unfounded, and show that our original analysis and conclusions are well supported. Though the GC skew method does have a detection limit, we provide new evidence that the fundamental assumptions of our model are accurate, and introduce an improved GC skew calculation which correctly identified 100% of the authors gene inversions. Our new findings indicate that the trends we originally identified are stronger than they initially appeared: across species, 89-96% of lagging strand genes appear to be natively leading strand genes that changed orientation. Our statistical analyses offer further support for the notion that for some genes, the lagging strand orientation can be adaptive.

中文翻译：

---

响应 不支持细菌基因组中滞后 9 链编码的适应性假设

我们小组之前的几项研究表明，正选择可以驱动某些而非全部基因保留在滞后链方向。这可能是多种因素的结果，包括通过复制和转录之间的冲突加速进化。Liu 和 Zhang 质疑这一观点，并声称我们检测基因倒位的方法存在缺陷。在这里，我们提供了经验证据，证明他们的批评在很大程度上是没有根据的，并表明我们的原始分析和结论得到了很好的支持。尽管 GC 偏斜方法确实有检测限，但我们提供了新的证据证明我们模型的基本假设是准确的，并引入了改进的 GC 偏斜计算，可以正确识别 100% 的作者基因倒位。我们的新发现表明，我们最初确定的趋势比最初出现的趋势更强：跨物种，89-96% 的滞后链基因似乎是改变方向的天然领先链基因。我们的统计分析为某些基因的滞后链方向可以具有适应性的观点提供了进一步的支持。