Segmentation clock gene pairing drives robust pattern formation

Gene expression is an inherently stochastic process (1,2); however, organismal development and homeostasis require that cells spatiotemporally coordinate the expression of large sets of genes. Coexpressed gene pairs in metazoans often reside in the same chromosomal neighborhood, with gene pairs representing 10% - 50% of all genes depending on species (3–6). As shared upstream regulators can ensure correlated gene expression, the selective advantage of maintaining adjacent gene pairs remains unknown (6). Here, using two linked zebrafish segmentation clock genes, her1 and her7, and combining single-cell transcript counting, genetic engineering, real-time imaging and computational modeling, we reveal that gene pairing boosts correlated transcription and provides phenotypic robustness for developmental pattern formation. Our results demonstrate that disrupting gene pairing disrupts oscillations and segmentation, identifying the selective pressure retaining correlated transcription to sustain a robust and rapid developmental clock. We anticipate that these findings will inspire investigating advantages of gene pairing in other systems and engineering precise synthetic clocks in embryos and organoids.