Agouti-related peptide 2 facilitates convergent evolution of stripe patterns across cichlid fish radiations

The color patterns of African cichlid fishes provide notable examples of phenotypic convergence. Across the more than 1200 East African rift lake species, melanic horizontal stripes have evolved numerous times. We discovered that regulatory changes of the gene agouti-related peptide 2 (agrp2) act as molecular switches controlling this evolutionarily labile phenotype. Reduced agrp2 expression is convergently associated with the presence of stripe patterns across species flocks. However, cis-regulatory mutations are not predictive of stripes across radiations, suggesting independent regulatory mechanisms. Genetic mapping confirms the link between the agrp2 locus and stripe patterns. The crucial role of agrp2 is further supported by a CRISPR-Cas9 knockout that reconstitutes stripes in a nonstriped cichlid. Thus, we unveil how a single gene affects the convergent evolution of a complex color pattern.非洲慈鲷的体色图案，是表型趋同演化的经典范例。在东非裂谷湖域的1200余种慈鲷中，黑色水平条纹已独立演化出现数十次。本研究发现，刺鼠相关肽2基因(agouti-related peptide 2, agrp2)的调控变异可作为分子开关，调控这一易随演化改变的表型。在各物种类群中，agrp2表达量的下调与条纹图案的出现呈趋同关联。但跨辐射演化类群而言，顺式调控突变无法预测条纹性状的出现，提示其调控机制存在独立性。遗传定位实验证实了agrp2基因座与条纹图案之间的关联。CRISPR-Cas9基因敲除实验可在无条纹的慈鲷中重建条纹表型，进一步佐证了agrp2的关键作用。综上，本研究揭示了单个基因如何调控复杂体色图案的趋同演化。