Grandchamp, A.; Lebherz, M. K.; Dohmen, E.

De novo gene emergence refers to the process by which new genes arise from mutations in previously non-coding genomic regions. Prior to becoming fixed in a species, newly expressed open reading frames (neORFs) undergo significant turnover within their species of origin. Investigating these early stages of de novo gene emergence is essential for understanding the mechanisms that enable gene formation from scratch. No software currently exists that can identify and characterise novel, unannotated open reading frames from a transcriptome, and analyse their mutations and fixation patterns within or across species. To address this gap, we introduce DESwoMA (De novo Emergence Study With Outgroup MutAtioNs), a software tool designed to: (1) detect neORFs in transcriptomes, (2) filter neORFs with no homology to outgroup genes, and (3) search for syntenic sequences homologous to neORFs in outgroup genomes (and optionally transcriptomes) and analyse mutations in coding features between these sequences. We applied DESwoMAN with two different strategies to three setups, using twice human and once fruit fly as query species. Our results highlight the tool\'s capabilities and demonstrate its potential for elucidating the early stages of de novo gene emergence. DESwoMAN is available at https://github.com/AnnaGrBio/DESWOMAN. It is implemented in Python3 and comes with a docker image on DockerHub for easy installation and execution including all (non-Python) dependencies.