GenEra can uncover deeper evolutionary relationships compared with previously published methods [24, 35], as seen in the number of genes that are traced back to the LUCA (cellular organisms). Using GenEra with additional 6-frame genome searches reduces the number of TRGs in the youngest taxonomic levels, from the species level up to the genus level, but older taxonomic levels are unaffected when including protein-against-genome data. Using JackHMMER increases the sensitivity at detecting homologs within older taxonomic levels, but shows little effect at finding homologs in the youngest taxonomic levels. Foldseek also increases the sensitivity at older levels but overestimates the number of genes at the species and genus levels.
