Marand Alexandre P, Jiang Luguang, Gomez-Cano Fabio, Minow Mark A A, Zhang Xuan, Mendieta John P, Luo Ziliang, Bang Sohyun, Yan Haidong, Meyer Cullan, Schlegel Luca, Johannes Frank, Schmitz Robert J
Department of Genetics, University of Georgia, Athens, GA, USA.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Science. 2025 Apr 18;388(6744):eads6601. doi: 10.1126/science.ads6601.
Gene expression and complex phenotypes are determined by the activity of cis-regulatory elements. However, an understanding of how extant genetic variants affect cis regulation remains limited. Here, we investigated the consequences of cis-regulatory diversity using single-cell genomics of more than 0.7 million nuclei across 172 (maize) inbreds. Our analyses pinpointed cis-regulatory elements distinct to domesticated maize and revealed how historical transposon activity has shaped the cis-regulatory landscape. Leveraging population genetics principles, we fine-mapped about 22,000 chromatin accessibility-associated genetic variants with widespread cell type-specific effects. Variants in TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR-binding sites were the most prevalent determinants of chromatin accessibility. Finally, integrating chromatin accessibility-associated variants, organismal trait variation, and population differentiation revealed how local adaptation has rewired regulatory networks in unique cellular contexts to alter maize flowering.
基因表达和复杂表型由顺式调控元件的活性决定。然而，对于现存遗传变异如何影响顺式调控的理解仍然有限。在这里，我们通过对172个（玉米）自交系中超过70万个细胞核进行单细胞基因组学研究，调查了顺式调控多样性的后果。我们的分析确定了驯化玉米特有的顺式调控元件，并揭示了历史转座子活性如何塑造了顺式调控景观。利用群体遗传学原理，我们精细定位了约22000个与染色质可及性相关的遗传变异，这些变异具有广泛的细胞类型特异性效应。TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR结合位点的变异是染色质可及性最普遍的决定因素。最后，整合与染色质可及性相关的变异、生物体性状变异和群体分化，揭示了局部适应如何在独特的细胞环境中重新连接调控网络，从而改变玉米开花。
