An evolutionary perspective of Intronless Genes highlight their recent highly specialized role  

Short Abstract:  Eukaryotic genes without introns in their coding sequence are known as "single-exon genes" (SEGs), in contrast to "multiple exon genes'' (MEGs). Intronless genes (IGs), are a subgroup of SEGs additionally characterized by the lack of introns in their UTRs. IGs are inherently involved in development, growth, and cell proliferation. Because of their prokaryotic architecture, IGs in eukaryotic genomes, provide interesting datasets for computational analysis in comparative genomics and evolutionary trajectories. Comparative analysis of their sequences among genomes can help to identify the unique and conserved features in these genes, and hence provide insight into intron's role in gene evolution and a better understanding of genome architecture and arrangement. Several diseases such as Williams Beuren syndrome, myoclonus epilepsy, neuroblastoma, Alzheimer and cancer have been linked to proteins encoded by IGs. This work aimed to determine the evolutionary history of IGs encoding proteins in the mouse (Mus musculus) genome. Mouse IGs and MEGs datasets were obtained from the Ensembl database according to their exon and transcript count. We predicted 1116 protein-coding IGs from the Mouse genome. Mouse peptide sequences were submitted to ProteinOrtho that allowed the inference of gene orthologs relationships in 10 genomes, including Homo sapiens. From ProteinOrtho’s predictions, orthology graphs were constructed, and an in-house developed method called Best Match Graph Modular Decomposition (BMGMD) was used. This method performs a modular decomposition of the orthology graphs and infers the gene trees that are consistent with the species phylogeny. Furthermore, each internal node of these trees represents a duplication or speciation event. Subsequently, the gene trees are reconciled with the species tree to determine in which branch of the species tree events occur and, at the same time, infer gene losses. This method also allows us to estimate how ancestral a gene family is and to identify species-specific genes. Further, we selected those orthologs that were conserved as IGs in other genomes. Protein orthologs among 10 genomes confirmed a high conservancy of IGs associated with the regulation of neurobiological processes in Vertebrata and with chromatin condensation in more distant organisms. Overall, our results support the hypothesis that IGs are “recent” highly specialized genes that are transcribed skipping splicing events entailing a higher transcriptional fidelity and saving cell energy waste during essential/housekeeping pathways.