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.