Decoding Alignment-Independent Retinal Regulatory Codes in Vertebrate Genomes

Homologous cell types have been conserved in animals over more than a hundred million years of evolution. Comparative genomics has identified orthologous genes and conserved non-coding regions through aligning sequences across species. Nevertheless, the sequences within non-coding regulatory elements often change over time in a nearly neutral manner, even when their regulatory functions remain unchanged. As a result, it has become challenging to find homologous functional non-coding sequences across species. To address this apparent paradox, we focus on the vertebrate retina as a model system and examined the single-cell-level chromatin accessibility landscape in the retinas of lamprey, zebrafish, goldfish, bullfrog, chicken, lizard, mouse, and human. We identified conserved sets of transcription factor binding motifs (i.e., regulatory codes) in each of six major retinal cell groups approximately since the origin of vertebrates. In this seminar, I will present current efforts to compare photoreceptor cell groups in higher resolution across species. Vertebrate photoreceptor cells are primarily classified into two groups: rods, which enable scotopic vision, and cones, which facilitate daylight vision. Rods and cones are further subdivided into eight distinct subtypes, each defined by its spectral sensitivities, morphology, and function. Our latest analyses reveal that regulatory codes in the eight photoreceptor types converge into four supertypes conserved across diverse species. These results would offer a format for studying regulatory homology when the underlying sequences are no longer directly comparable.

Yohei Ogawa is a Project Assistant Professor at the National Institute of Genetics, Japan. During his PhD at the University of Tokyo, he studied photoreceptor differentiation in zebrafish and identified several transcription factors that specify the cell-type identity of the middle-wave-sensitive cone photoreceptor cells. He then joined Dr. Joseph C. Corbo’s laboratory as a postdoctoral researcher at Washington University School of Medicine in St. Louis, USA, where he spent 6 years investigating the retinal cis-regulatory codes across vertebrate species using single-nuclei chromatin accessibility profiling and machine-learning-based regulatory sequence analysis. Back in Japan and joining Dr. Kuraku’s lab at the National Institute of Genetics, he is now exploring how repeat landscapes shape the organization of vertebrate genomes and the evolutionary constraints on the genome.

[Host: Paulo Pereira, Evolutionary Genetics and Genomics - EVOLGEN]