Cis- and Trans-Regulatory Variations in the Domestication of the Chili Pepper Fruit

The process of domestication requires the rapid transformation of the wild morphology into the cultivated forms that humans select for. This process often takes place through changes in the regulation of genes, yet, there is no definite pattern on the role of cis- and trans-acting regulatory variations in the domestication of the fruit among crops. Using allele-specific expression and network analyses, we characterized the regulatory patterns and the inheritance of gene expression in wild and cultivated accessions of chili pepper, a crop with remarkable fruit morphological variation. We propose that gene expression differences associated to the cultivated form are best explained by cis-regulatory hubs acting through trans-regulatory cascades. We show that in cultivated chili, the expression of genes associated with fruit morphology is partially recessive with respect to those in the wild relative, consistent with the hybrid fruit phenotype. Decreased expression of fruit maturation and growth genes in cultivated chili suggest that selection for loss-of-function took place in its domestication. Trans-regulatory changes underlie the majority of the genes showing regulatory divergence and had larger effect sizes on gene expression than cis-regulatory variants. Network analysis of selected cis-regulated genes, including ARP9 and MED25, indicated their interaction with many transcription factors involved in organ growth and fruit ripening. Differentially expressed genes linked to cis-regulatory variants and their interactions with downstream trans-acting genes have the potential to drive the morphological differences observed between wild and cultivated fruits and provide an attractive mechanism of morphological transformation during the domestication of the chili pepper.