Controlling gene function with dual-coding exons: Exploring patterns of conservation and expression

Genes are comprised of exons, which are encoded in groups of three called codons. Each codon corresponds to a particular amino acid, and the chain of amino acids makes a protein product. Genes can encode different protein products through a mechanism called alternative splicing, which typically uses different subsets of those exons. Alternative splicing impacts the proteins that are produced in different tissues or developmental timepoints; changes to an exon can cause errors in a subset of these proteins, which is the source of some genetic diseases and cancers. The research here investigates a relatively unrecognized form of alternative splicing in which a single exon encodes two alternative protein products. This happens when the exon boundary is shifted by one or two nucleotides, resulting in different codons. Previously thought to be a rare phenomenon in the human genome, recent work in our lab has found that ~13% of human genes show evidence of this dual-coding function. We investigated the conservation of the dual-coding nature of these exons, finding that they are highly conserved in mammals. This research seeks to further contextualize the alternative reading frame (ARF) variants of dual-coding exons by determining their tissue-specific expression level in RNA sequence data. Using a combination of preexisting tools and custom scripts we investigated the expression levels of the ARF variants in a dataset of RNA sequences sampled from 13 tissue types across 714 individuals, and found that both variants were present at high levels in various tissues. We further investigated the relative abundance of the variants. The identification of genes containing ARFs which occur more frequently in a particular tissue will allow for further analysis on the potential relationship between it and specific diseases