Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay

Abstract

Nucleotide sequences along a gene provide instructions to transcriptional and cotranscriptional machinery allowing genome expansion into the transcriptome. Nucleotide sequence can often be shared between two genes and in some occurrences, a gene is located completely within a different gene; these are known as host/nested gene pairs. In these instances, if both genes are transcribed, overlap can result in a transcriptional crosstalk where genes regulate each other. Despite this, a comprehensive annotation of where such genes are located and their expression patterns is lacking. To address this, we provide an up-to-date catalog of host/nested gene pairs in mouse and human, showing that over a tenth of all genes contain a nested gene. We discovered that transcriptional co-occurrence is often tissue specific. This coexpression was especially prevalent within the transcriptionally permissive tissue, testis. We use this developmental system and scRNA-seq analysis to demonstrate that the coexpression of pairs can occur in single cells and transcription in the same place at the same time can enhance the transcript diversity of the host gene. In agreement, host genes are more transcript-diverse than the rest of the transcriptome. Host/nested gene configurations are common in both human and mouse, suggesting that interplay between gene pairs is a feature of the mammalian genome. This highlights the relevance of transcriptional crosstalk between genes which share nucleic acid sequence. The results and analysis are available on an Rshiny application (https://hngeneviewer.sites.er.kcl.ac.uk/hn_viewer/).