The influence of pleiotropy on adaptive responses is a highly controversial topic, with limited empirical evidence available. Recognizing the pivotal role of the correlation of fitness effects, we designed an experiment to compare the adaptive gene expression evolution of natural and experimental populations. To test this, we studied the evolution of gene expression in response to temperature in two Drosophila species on a natural temperature cline in North America and replicated populations evolving in hot- and cold-temperature regimes. If fitness effects of affected traits are independent, pleiotropy is expected to constrain the adaptive response in both settings, laboratory and natural populations. However, when fitness effects are more correlated in natural populations, adaptation in the wild will be facilitated by pleiotropy. Remarkably, we find evidence for both predicted effects. In both settings, genes with strong pleiotropic effects contribute less to adaptation, indicating that the majority of fitness effects are not correlated. In addition, we discovered that genes involved in adaptation exhibited more pleiotropic effects in natural populations. We propose that this pattern can be explained by a stronger correlation of fitness effects in nature. More insights into the dual role of pleiotropy will be crucial for the understanding of polygenic adaptation. The role of pleiotropy in adaptation has long been a subject of controversy. In this study, we propose a novel approach to address the crucial question of the correlation of fitness effects by comparing the evolutionary responses of gene expression to temperature in natural and experimental populations. Our findings reveal a dual effect of pleiotropy, shedding light on the correlation of fitness effects. Consistent with previous results, we demonstrate that genes with higher levels of pleiotropy exhibit a reduced evolutionary response compared to genes with lower levels of pleiotropy. This pattern implies that the majority of fitness effects are weakly, if at all, correlated. Furthermore, our study discovered an intriguing result: Pleiotropy actually facilitates adaptation in natural populations. This suggests that in nature, certain traits experience correlated fitness effects, likely driven by correlated environmental variables. Understanding the dual role of pleiotropy is a crucial step in unraveling the mechanisms behind polygenic adaptation. By deciphering its complex dynamics, we gained profound insights into how organisms adapt to changing environments.
