A revisit to universal single-copy genes in bacterial genomes

Universal single-copy genes (USCGs) are widely used for species classification and taxonomic profiling. Despite many studies on USCGs, our understanding of USCGs in bacterial genomes might be out of date, especially how different the USCGs are in different studies, how well a set of USCGs can distinguish two bacterial species, whether USCGs can separate different strains of a bacterial species, to name a few. To fill the void, we studied USCGs in the most updated complete bacterial genomes. We showed that different USCG sets are quite different while coming from highly similar functional categories. We also found that although USCGs occur once in almost all bacterial genomes, each USCG does occur multiple times in certain genomes. We demonstrated that USCGs are reliable markers to distinguish different species while they cannot distinguish different strains of most bacterial species. Our study sheds new light on the usage and limitations of USCGs, which will facilitate their applications in evolutionary, phylogenomic, and metagenomic studies.