Ascensao Joao A, Abedi Keon D, Prasad Aditya N, Hallatschek Oskar
Department of Bioengineering, University of California Berkeley, CA, USA.
Present affiliation: Department of Organismic and Evolutionary Biology, Harvard University, MA, USA.
bioRxiv. 2025 Aug 21:2025.08.18.670924. doi: 10.1101/2025.08.18.670924.
In simple microbial populations, the fitness effects of most selected mutations are generally taken to be constant, independent of genotype frequency. This assumption underpins predictions about evolutionary dynamics, epistatic interactions, and the maintenance of genetic diversity in populations. Here, we systematically test this assumption using beneficial mutations from early generations of the Long-Term Evolution Experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in approximately 80% of strain pairs tested. Most competitions exhibit negative frequency-dependence, where fitness advantages decline as mutant frequency increases. Furthermore, we demonstrate that the strength of frequency-dependence is predictable from invasion fitness measurements, with invasion fitness explaining approximately half of the biological variation in frequency-dependent slopes. Additionally, we observe violations of fitness transitivity in several strain combinations, indicating that competitive relationships cannot always be predicted from fitness relative to a single reference strain alone. Through high-resolution measurements of within-growth cycle dynamics, we show that simple resource competition explains a substantial portion of the frequency-dependence: when faster-growing genotypes dominate populations, they deplete shared resources more rapidly, reducing the time available for fitness differences to accumulate. Our results demonstrate that even in a simple model system designed to minimize ecological complexity, subtle ecological interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary dynamics.
在简单的微生物群体中，大多数被选择突变的适应性效应通常被认为是恒定的，与基因型频率无关。这一假设支撑着有关进化动力学、上位性相互作用以及群体中遗传多样性维持的预测。在此，我们使用长期进化实验（LTEE）早期世代的有益突变，系统地检验了这一假设。通过基于流式细胞术的竞争试验，我们发现频率依赖的适应性效应是常态而非例外，在所测试的约80%的菌株对中都会出现。大多数竞争表现出负频率依赖性，即随着突变体频率增加，适应性优势会下降。此外，我们证明频率依赖性的强度可从入侵适应性测量中预测出来，入侵适应性解释了频率依赖斜率中约一半的生物学变异。另外，我们在几种菌株组合中观察到了适应性传递性的违反情况，这表明竞争关系不能总是仅从相对于单个参考菌株的适应性来预测。通过对生长周期内动态的高分辨率测量，我们表明简单的资源竞争解释了频率依赖性的很大一部分：当生长较快的基因型在群体中占主导时，它们会更快地耗尽共享资源，减少了适应性差异积累所需的时间。我们的结果表明，即使在一个旨在最小化生态复杂性的简单模型系统中，密切相关基因型之间微妙的生态相互作用也会产生频率依赖的选择，从而可能从根本上改变进化动力学。
