Forsberg Simon K G, Melo Diogo, Wolf Scott W, Grenier Jennifer K, Tang Minjia, Henry Lucas P, Pallares Luisa F, Clark Andrew G, Ayroles Julien F
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2025 Jun 24;122(25):e2410452122. doi: 10.1073/pnas.2410452122. Epub 2025 Jun 18.
Evolutionary adaptation to new environments likely results from a combination of selective sweeps and polygenic shifts, depending on the genetic architecture of traits under selection. While selective sweeps have been widely studied, polygenic responses are thought to be more prevalent but remain challenging to quantify. The infinitesimal model makes explicit the hypothesis about the dynamics of changes in allele frequencies under selection, where only allelic effect sizes, frequencies, linkage, and gametic disequilibrium matter. Departures from this, like long-range correlations of allele frequency changes, could be a signal of epistasis in polygenic response. We performed an Evolve & Resequence experiment in exposing flies to a high-sugar diet for over 100 generations. We tracked allele frequency changes in >3000 individually sequenced flies and population pools and searched for loci under selection by identifying sites with allele frequency trajectories that differentiated selection regimes consistently across replicates. We estimate that at least 4% of the genome was under positive selection, indicating a highly polygenic response. The response was dominated by small, consistent allele frequency changes, with few loci exhibiting large shifts. We then searched for signatures of selection on pairwise combinations of alleles in the new environment and found several strong signals of putative epistatic interactions across unlinked loci that were consistent across selected populations. Finally, we measured differentially expressed genes (DEGs) across treatments and show that DEGs are enriched for selected SNPs. Our results suggest that epistatic contributions to polygenic selective response are common and lead to detectable signatures.
对新环境的进化适应可能源于选择性清除和多基因变化的结合，这取决于选择性状的遗传结构。虽然选择性清除已得到广泛研究，但多基因反应被认为更为普遍，不过对其进行量化仍具有挑战性。无穷小模型明确了关于选择作用下等位基因频率变化动态的假设，在此假设中，只有等位基因效应大小、频率、连锁和配子不平衡起作用。与此不同的情况，如等位基因频率变化的长程相关性，可能是多基因反应中上位性的信号。我们进行了一项“进化与重测序”实验，让果蝇在高糖饮食条件下繁殖超过100代。我们追踪了3000多只单独测序的果蝇以及群体样本中等位基因频率的变化，并通过识别等位基因频率轨迹能在各重复样本中一致区分选择模式的位点来寻找受选择的基因座。我们估计至少4%的基因组处于正选择之下，这表明存在高度多基因反应。这种反应主要由小的、一致的等位基因频率变化主导，很少有基因座表现出大的变化。然后我们在新环境中搜索等位基因对组合上的选择特征，发现了几个跨非连锁基因座的假定上位性相互作用的强信号，这些信号在所选群体中是一致的。最后，我们测量了不同处理之间的差异表达基因（DEG），并表明DEG在选定的单核苷酸多态性（SNP）中富集。我们的结果表明，上位性对多基因选择反应的贡献很常见，并导致可检测的特征。
