Genomic evidence for the importance of gene expression at transcription
level in determining mammalian phenotypes
Ben-Yang Liao and Meng-Pin Weng
National Health Research Institutes, Taiwan.
Protein coding genes need to be transcribed into mRNA molecules to function
in the cell. Since early 1970s, the presence/abundance of mRNA production
in a cell type or tissue has been considered as an indication of gene
function in the anatomical entities where the mRNA found, and methods
for visualizing mRNA expression such as mRNA in situ hybridization have
become part of the standard repertoire of neuroscience and developmental
biology. In spite of the importance and prevalence of abovementioned
approach in biological investigations, an important assumption for such
practice that a gene’s locations of mRNA production determines its
responsible phenotypes has never been verified systematically and
genome-widely. In the present study, we analyzed mRNA expression data
(including those derived from microarrays, RNA-seq and mRNA in situ
hybridization) with the combination of documented mutant phenotype data
of mouse genes at genome-scale, and found that gene expression at mRNA
level correspond to the manifested organs with dysfunctions when the gene
is mutated or deleted from the genome. Highly expressed genes, genes
expressed in early embryonic stages, and genes encoding non-secretory
proteinshave higher expression-phenotype correspondence in general.
In addition, genes with greater expression-phenotype correspondence tend
to evolve slowly. Our study provides the first genomic evidence for the
importance of gene expression at transcription level in determining
mammalian phenotypes. Mammalian transcriptomes are constrained by neutral
selection during evolution likely due to the direct impact of mRNA
expression on phenotypes.