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 tothe evolutionary time-scale separating the two species, some physiological functions involvedin vision differ between the two species. Here, public RNA-seq data sets were used tointerrogate genome-wide gene expression patterns in mouse and human retina and retinalpigment epithelium in order to identify genes of significance underlying visual signalprocessing in the two species. Individual genes with distinct and conserved expression patternsacross the retinal tissues were identified both within and between species, followed by anassessment of biomedical roles in visual functions, and their extent of sequence conservationamong mammals. There was evidence that the conservation of expression patterns is linked toevolutionary sequence conservation, retinal cell-type specificity and disease association,suggesting that these parameters should be considered together when investigating the geneticand evolutionary underpinnings of mammalian eye function and pathology. The extent ofsequence and expression pattern conservation observed at individual genes and at pathway levelcould highlight the relative importance of signaling pathways that control retinal celldevelopment, differentiation and survival across species. This information may be crucial inproviding the basis for which genes to prioritize in cross-species treatment testing, includinggene therapy for retinal diseases, as well as providing deeper insights on the evolution of retinaldiseases susceptibilities in different species.