Bacillus safensis strains have emerged as versatile microbial platforms for bioproduction, combining the benefits of probiotic utility and biocontrol. In this study, we describe the isolation and in-depth characterization of a previously unreported B. safensis strain, LG01. The genome of this strain comprises a circular chromosome encoding 13 secondary metabolite biosynthetic gene clusters, 144 carbohydrate-active enzymes, 2 antibiotic resistance loci, and 1 prophage region, indicative of strong antimicrobial and metabolic capacity. Its protein secretion systems support nutrient acquisition, colonization, quorum sensing, and antibiotic synthesis. Our phenotypic assays confirmed the antifungal and antibacterial activity, proteolytic and cellulolytic functions, and robust biofilm formation of the strain. By performing a comparative genomic analysis, we identified 78 strain-specific genes enriched in the bacteriocin immunity and sporulation pathways. Signals of positive selection in the membrane and transcriptional regulator genes further reflect the adaptive evolution underlying the strain’s ecological fitness. Together, these findings advance our understanding of the genomic features of B. safensis LG01 and highlight its promise as a candidate for biocontrol and probiotic applications.

Papillomaviruses (PVs) are groups of ubiquitous DNA viruses infecting a wide range of vertebrate hosts, including human. The infection of some human PVs (i.e., HPVs) are strongly associated with cancers, but it remains elusive how such pathogenicity evolved at the genomic level. Here we performed a super-pangenome analysis on a compendium of well-curated 3562 human and animal PV genomes. We found their global genomic diversity being strongly associated with their body sites and tissue origins, but not with their host, geographical, or disease specificity. By reconciling time-resolved phylogenies of PVs and their hosts, we revealed a high-resolution view on how virus-host cospeciation, horizontal host switches, and duplication/loss turnovers collectively shaped the evolution of PVs. We identified key selection-driven mutations that defined the genus-specific divergence of PVs, with those underlying the rise of Alpha-PVs highly enriched in the N-terminal domain of E1 gene. Especially, we identified a group of risk-defining variant sites showing contrasting genotypes between low-risk and high-risk HPVs. With four independent PV genome cohorts, we further validated their high sensitivity and specificity on HPV risk classification even at single site level, underscoring their application values in large-scale HPV screening tests. Finally, with cervical and oropharyngeal cancer patient cohorts assembled by this study, we also evaluated the prognostic value of specific HPV16 variants in predicting patient survival. Taken together, such illumination on the genome and pathogenicity evolution of PVs paves the road for better prevention, control, and treatment of PV-related cancers. Significance statement: Papillomaviruses (PVs) are ancient and widespread DNA viruses co-evolved with many vertebrate hosts, including human. Some human PVs (e.g., HPV16 and HPV18) bear strong association with cancers, raising a pressing public health challenge. A better understanding of how such pathogenicity evolved holds the key in addressing this challenge. Here we systematically investigated the genomic and evolutionary diversity of PVs via a pangenome study on over 3500 human and animal PV isolates, which revealed key selection-driven mutations shaping their genome and pathogenicity evolution. With independently acquired HPV-associated cancer cohorts, we further demonstrated how some of these important HPV variants can serve as clinically informative predictive and prognostic biomarkers. Such comprehensive characterization on PVs’ genome diversity, pathogenicity evolution, and clinical implication paves the road for better prevention, control, and treatment of PV-related cancers.

Variation in telomere length, sequence composition and epigenetic state influences genome stability, aging and disease, yet its high-resolution characterization across species remains challenging. Here we present TeloXplorer, a computational framework for long-read data that jointly profiles telomere length, telomere variant repeats (TVRs) and DNA methylation at chromosome-end and haplotype resolution. Across simulated and empirical datasets from humans, Arabidopsis and yeast, TeloXplorer accurately resolved chromosome-end-specific telomere features and highlighted the importance of sample-matched, haplotype-resolved assemblies. Analysis of two human trios revealed concordant relative telomere-length profiles, predominantly Mendelian transmission of TVR haplotypes and family-conserved methylation patterns. Across 232 individuals from the Human Pangenome Reference Consortium, chromosome-end telomere-length rankings were conserved across five continental and 28 population groups. High-accuracy reads from 73 individuals further revealed elevated TVR haplotype diversity among individuals of African ancestry, together with extensive interchromosomal sharing and duplication of TVR architectures. Subtelomeric TAR1 elements were strongly associated with local DNA methylation and telomere motif diversity. Together, these analyses provide a multidimensional atlas of telomere diversity across species, chromosome ends, haplotypes and populations, revealing how telomere architecture varies and is inherited across biological scales.