Gene duplication and cross-regulation generates regulatory network diversity in Arabidopsis

Abstract

Duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, I examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures. In addition, the cytokinin signaling system in Arabidopsis is regulated by redundant response regulators (ARRs), 11 positively-acting (type-B) and ten negatively-acting (type-A). Here, I suggest that the multiple negative feedback ARR pairs function synergistically and are cross-regulated, forming highly diverse types of multilayered, hierarchical regulatory network structures with abilities to control dynamic patterns of gene expression. Accordingly, deletion or induction of a type-B ARR from the system altered dynamic expression patterns of type-A ARRs. Our results suggest that network rewiring through cross-linked regulation of multiply-redundant genes is a fundamental evolutionary strategy to provide regulatory diversity to cellular signaling systems.