Tuberculosis (TB) remains a leading infectious killer, with growing evidence that the human microbiome—particularly in the gut and lungs—shapes susceptibility, progression, and treatment outcomes. ...

By solving a previously unsolved biological question, the AI co-scientist predicted a complex mechanism of gene transfer and generated hypotheses that opened new research directions, illustrating AI's...

Capsid-forming PICIs (cf-PICIs) produce their own capsids and exploit phage tails from unrelated species to transfer their DNA across bacterial hosts. This tail piracy enables broad dissemination and ...

Society journals are deeply rooted in our scientific community and a vital part of it. They serve as a venue for the publication of high-quality articles while promoting the mission-driven activities ...

Understanding the genetic basis of ecological adaptation is a fundamental challenge of evolutionary biology, often limited by the availability of diverse and curated datasets. Spirochaetes are widely distributed, ancient bacteria found in diverse environments, offering a unique opportunity to explore ecological transitions. Despite their high diversity and the presence of globally important pathogens such as syphilis (Treponema spp.), Lyme disease (Borrelia spp.), or leptospirosis (Leptospira spp.), Spirochaetes remain poorly characterized as a phylum. Moreover, the recent discovery of non-spiral lineages has broadened its complexity and require a re-evaluation of the entire phylum s evolution. Here, we present the most comprehensive phylogenomic and functional analysis of Spirochaetes, examining a curated dataset of 172 spirochaetal genomes representing all cultivable spirochete species. Our robust phylogenetic framework revisits the evolutionary rooting of this phylum and reveals that the Last Spirochaetal Common Ancestor (LSCA) diverged into two major clades, with Brachyspira species diverging early from the rest of Spirochaetes. Ancestral genome reconstruction showed that the LSCA was a motile, endoflagellated bacterium with a heterotrophic metabolism, shedding light on the biology of one of the most anciently diverging bacterial phyla. Functional analysis revealed genomic signatures associated with key phenotypic adaptations within Spirochaetes, such as independent loss of the characteristic spiral morphology and emergence of host-associated lineages. Notably, we found that loss of endoflagellar genes correlated with the appearance of non-spiral species. Lastly, we employed phylogenetic profiling to identify previously uncharacterized motility-associated gene families, whose role was then demonstrated experimentally. Overall, this study provides new evolutionary insights into how ecological specialization has shaped spirochete genomes, offering a framework to elucidate further the mechanisms driving key evolutionary transitions in this clinically relevant phylum. ### Competing Interest Statement The authors have declared no competing interest.