Brain-related genes are specifically enriched with long phase 1 introns.

Intronic gene regions are mostly considered in the scope of gene expression regulation, such as alternative splicing. However, relations between basic statistical properties of introns are much rarely studied in detail, despite vast available data. Particularly, little is known regarding the relationship between the intron length and the intron phase. Intron phase distribution is significantly different at different intron length thresholds. In this study, we performed GO enrichment analysis of gene sets with a particular intron phase at varying intron length thresholds using a list of 13823 orthologous human-mouse gene pairs. We found a specific group of 153 genes with phase 1 introns longer than 50 kilobases that were specifically expressed in brain, functionally related to synaptic signaling, and strongly associated with schizophrenia and other mental disorders. We propose that the prevalence of long phase 1 introns arises from the presence of the signal peptide sequence and is connected with 1-1 exon shuffling.