De Novo Origin of Protein-Coding Genes in Murine Rodents

Background: New genes in eukaryotes are created through a variety of different mechanisms. De novo origin from non-coding DNA is a mechanism that has recently gained attention. So far, de novo genes have been described in a handful of organisms, with Drosophila being the most extensively studied. We searched for genes that have appeared de novo in the mouse and rat lineages. Methodology: Using a rigorous and conservative approach we identify 75 murine genes (69 mouse genes and 6 rat genes) for which there is good evidence of de novo origin since the divergence of mouse and rat. Each of these genes is only found in either the mouse or rat lineages, with no candidate orthologs nor evidence for potentially-unannotated orthologs in the other lineage. The veracity of each of these genes is supported by expression evidence. Additionally, their presence in one lineage and absence in the other cannot be explained by sequencing gaps. For 11 of the 75 candidate novel genes we could identify a mouse-specific mutation that led to the creation of the open reading frame (ORF) specifically in mouse. None of the six rat-specific genes had an unequivocal rat-specific mutation creating the ORF, which may at least be partly due to lower data quality for that genome. Conclusions: All 75 candidate genes presented in this study are relatively small and encode short peptides. A large number of them (51 out of 69 mouse genes and 3 out of 6 rat genes) also overlap with other genes, either within introns, or on the opposite strand. These characteristics have previously been documented for de novo genes. The description of these genes opens up the opportunity to integrate this evolutionary analysis with the rich experimental data available for these two model organisms.