Integrative human-mouse gene expression and phylogenetics analysis to prioritize genes of evolutionary and biomedical importance in the retina and retinal pigment epithelium

Abstract

Mammalian models, such as mice, are often used to study human retinal diseases, but, owing to the evolutionary time-scale separating the two species, some physiological functions involved in vision differ between the two species. Here, public RNA-seq data sets were used to interrogate genome-wide gene expression patterns in mouse and human retina and retinal pigment epithelium in order to identify genes of significance underlying visual signal processing in the two species. Individual genes with distinct and conserved expression patterns across the retinal tissues were identified both within and between species, followed by an assessment of biomedical roles in visual functions, and their extent of sequence conservation among mammals. There was evidence that the conservation of expression patterns is linked to evolutionary sequence conservation, retinal cell-type specificity and disease association, suggesting that these parameters should be considered together when investigating the genetic and evolutionary underpinnings of mammalian eye function and pathology. The extent of sequence and expression pattern conservation observed at individual genes and at pathway level could highlight the relative importance of signaling pathways that control retinal cell development, differentiation and survival across species. This information may be crucial in providing the basis for which genes to prioritize in cross-species treatment testing, including gene therapy for retinal diseases, as well as providing deeper insights on the evolution of retinal diseases susceptibilities in different species.