Co-evolution of MAF and OTX transcription factors in relation to the evolution of rod photoreceptors in the retina

This repository contains the code and data for the following manuscript in review. Gene duplication and co-evolution of MAF and OTX family transcription factors shaped vertebrate rod photoreceptors Soumitra Pal, Noor D. White Carreiro, Zachary Batz, Anand Swaroop ABSTRACT Rod photoreceptors are essential for dim-light vision, and their specification and maintenance in the mammalian retina depend on the Maf-family bZIP transcription factor NRL. Pathogenic variants in NRL cause human retinal degenerative diseases, underscoring the importance of understanding its evolutionary origin and regulation. Notably, several non-mammalian vertebrates possess NRL-independent rods, and paralogs such as MAFA and MAFB have been implicated in their development, motivating a deeper investigation into the evolution of the MAF transcription factor family. To address this, we curated MAF transcription factors across metazoans and reconstructed the evolutionary history of large and small MAFs. Our analyses show that both groups arose through ancient whole-genome duplications in vertebrates, and that the ancestral small MAF gene originated from an early duplication event predating chordate evolution. Mammalian NRL exhibits signatures of episodic positive selection, and markedly elevated expression compared to its non-mammalian counterparts. This upregulation is associated with a mammal-specific regulatory element that drives NRL expression in rods. Furthermore, the DNA-binding domain of mammalian NRL exhibits evidence of co-evolution with its key interacting OTX-family homeodomain protein CRX, suggesting coordinated adaptation of protein–DNA and protein–protein interactions critical for rod fate determination. Together, these findings establish an evolutionary framework for understanding how ancient duplication events shaped the MAF family and how NRL became central to stabilizing rod identity in mammals. Our study highlights both the deep conservation and plasticity of retinal regulatory networks, and points to future functional studies dissecting the emergence of NRL-dependent and NRL-independent mechanisms of rod development across vertebrates. Version history v0.0.1: An early version of the repository just to get the zenodo links.