Evolution of neuronal cell classes and types in the vertebrate retina

Abstract

The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs1. One might expect that retinal cell types evolved to accommodate these varied needs, but this has not been systematically studied. Here, we generated and integrated single-cell transcriptomic atlases of the retina from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a teleost fish, a bird, a reptile and a lamprey. Molecular conservation of the six retinal cell classes (photoreceptors, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells [RGCs] and Müller glia) was striking, with transcriptomic variation across species related to evolutionary distance. Major subclasses were also conserved, whereas variation among types within classes or subclasses was more pronounced. However, an integrative analysis revealed that numerous types are shared across species based on conserved gene expression programs that likely trace back to an early ancestral vertebrate. The degree of variation among types increased from the outer retina (photoreceptors) to the inner retina (RGCs), suggesting that evolution acts preferentially to shape the retinal output. Finally, we identified mammalian orthologs of midget RGCs, which comprise >80% of RGCs in the human retina, subserve high-acuity vision, and were believed to be primate-specific2; in contrast, the mouse orthologs have large receptive fields and comprise <2% of mouse RGCs. Projections of both primate and mouse orthologous types are overrepresented in the thalamus, which supplies the primary visual cortex. We suggest that midget RGCs are not primate innovations, but descendants of evolutionarily ancient types that decreased in size and increased in number as primates evolved, thereby facilitating high visual acuity and increased cortical processing of visual information.