美国冷泉港实验室Zachary B. Lippman小组在研究中取得进展。他们研究出隐性变异通过等级上位性促进植物表型变化。相关论文于2025年7月9日发表在《自然》杂志上。

在同源基因对的自然和工程顺式调控隐变的指导下，该课题组发现了额外的冗余反式调控，建立了一个控制番茄花序结构的调控网络。通过结合编码突变和顺式调控等位基因在分离所有网络基因的群体中，研究小组产生了216个基因型，跨越了广泛的花序复杂性，并在超过35000个花序中量化了分支。对这一高分辨率基因型-表型图谱的分析揭示了上位的层次模型，揭示了在平行对中存在一层剂量依赖的相互作用，增强了分支，最终产生了强大的协同效应。

然而，该研究团队也发现了平行对之间的拮抗层，即在一对中积累突变逐渐减少另一对中突变的影响。他们的研究结果表明，基因调控网络结构和来自平行多样化的复杂剂量效应如何汇聚在一起，形成表型空间，从而产生强烈缓冲表型和表型变化突然爆发的可能性。

据了解，隐性遗传变异单独发挥最小的表型效应，但被假设形成一个巨大的遗传多样性库，通过上位性相互作用驱动性状的进化。泛基因组学揭示了基因家族、顺式调控区域和调控网络中普遍存在的变异，从而使这一经典理论重新焕发了活力。由于难以处理的遗传学、有限的等位基因多样性和不充分的表型分辨率，测试隐性变异促进表型多样化的能力一直受到阻碍。

附：英文原文

Title: Cryptic variation fuels plant phenotypic change through hierarchical epistasis

Author: Zebell, Sophia G., Mart-Gmez, Carlos, Fitzgerald, Blaine, Cunha, Camila P., Lach, Michael, Seman, Brooke M., Hendelman, Anat, Sretenovic, Simon, Qi, Yiping, Bartlett, Madelaine, Eshed, Yuval, McCandlish, David M., Lippman, Zachary B.

Issue&Volume: 2025-07-09

Abstract: Cryptic genetic variants exert minimal phenotypic effects alone but are hypothesized to form a vast reservoir of genetic diversity driving trait evolvability through epistatic interactions1,2,3. This classical theory has been reinvigorated by pan-genomics, which is revealing pervasive variation within gene families, cis-regulatory regions and regulatory networks4,5,6. Testing the ability of cryptic variation to fuel phenotypic diversification has been hindered by intractable genetics, limited allelic diversity and inadequate phenotypic resolution. Here, guided by natural and engineered cis-regulatory cryptic variants in a paralogous gene pair, we identified additional redundant trans regulators, establishing a regulatory network controlling tomato inflorescence architecture. By combining coding mutations with cis-regulatory alleles in populations segregating for all four network genes, we generated 216 genotypes spanning a wide spectrum of inflorescence complexity and quantified branching in over 35,000 inflorescences. Analysis of this high-resolution genotype–phenotype map using a hierarchical model of epistasis revealed a layer of dose-dependent interactions within paralogue pairs enhancing branching, culminating in strong, synergistic effects. However, we also identified a layer of antagonism between paralogue pairs, whereby accumulating mutations in one pair progressively diminished the effects of mutations in the other. Our results demonstrate how gene regulatory network architecture and complex dosage effects from paralogue diversification converge to shape phenotypic space, producing the potential for both strongly buffered phenotypes and sudden bursts of phenotypic change.

DOI: 10.1038/s41586-025-09243-0

Source: https://www.nature.com/articles/s41586-025-09243-0