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Human papillomavirus type 18 (HPV18) and HPV45 account for approximately 20% of all cervix cancers. We show that HPV18, HPV45, and the recently discovered HPV97 comprise a clade sharing a most recent common ancestor within HPV α7 species. Variant lineages of these HPV types were classified by sequence analysis of the upstream regulatory region/E6 region among cervical samples from a population-based study in Costa Rica, and 27 representative genomes from each major variant lineage were sequenced. Nucleotide variation within HPV18 and HPV45 was 3.82% and 2.39%, respectively, and amino acid variation was 4.73% and 2.87%, respectively. Only 18 nucleotide variations, of which 10 were nonsynonymous, were identified among three HPV97 genomes. Full-genome comparisons revealed maximal diversity between HPV18 African and non-African variants (2.6% dissimilarity), whereas HPV18 Asian-American [E1 (AA)] and European (E2) variants were closely related (less than 0.5% dissimilarity); HPV45 genomes had a maximal difference of 1.6% nucleotides. Using a Bayesian Markov chain Monte Carlo (MCMC) method, the divergence times of HPV18, -45, and -97 from their most recent common ancestors indicated that HPV18 diverged approximately 7.7 million years (Myr) ago, whereas HPV45 and HPV97 split off around 5.7 Myr ago, in a period encompassing the divergence of the great ape species. Variants within the HPV18/45/97 lineages were estimated to have diverged from their common ancestors in the genus Homo within the last 1 Myr (<0.7 Myr). To investigate the molecular basis of HPV18, HPV45, and HPV97 evolution, regression models of codon substitution were used to identify lineages and amino acid sites under selective pressure. The E5 open reading frame (ORF) of HPV18 and the E4 ORFs of HPV18, HPV45, and HPV18/45/97 had nonsynonymous/synonymous substitution rate ratios (dN/dS) over 1 indicative of positive Darwinian selection. The L1 ORF of HPV18 genomes had an increased proportion of nonsynonymous substitutions (4.93%; average dN/dS ratio [M3] = 0.3356) compared to HPV45 (1.86%; M3 = 0.1268) and HPV16 (2.26%; M3 = 0.1330) L1 ORFs. In contrast, HPV18 and HPV16 genomes had similar amino acid substitution rates within the E1 ORF (2.89% and 3.24%, respectively), while HPV45 E1 was highly conserved (amino acid substitution rate was 0.77%). These data provide an evolutionary history of this medically important clade of HPVs and identify an unexpected divergence of the L1 gene of HPV18 that may have clinical implications for the long-term use of an L1-virus-like particle-based prophylactic vaccine. [ABSTRACT FROM AUTHOR]

We report the finished and annotated genome sequence of Aggregatibacter aphrophilus strain NJ8700, a strain isolated from the oral flora of a healthy individual, and discuss characteristics that may affect its dual roles in human health and disease. This strain has a rough appearance, and its genome contains genes encoding a type VI secretion system and several factors that may participate in host colonization. [ABSTRACT FROM AUTHOR]

The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whale-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the L1LD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncagenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incangruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophylctic across all genes. [ABSTRACT FROM AUTHOR]

Human papillomavirus 58 (HPV58) is found in 10 to 18% of cervical cancers in East Asia but is rather uncommon elsewhere. The distribution and oncogenic potential of HPV58 variants appear to be heterogeneous, since the E7 T20I/G63S variant is more prevalent in East Asia and confers a 7- to 9-fold-higher risk of cervical precancer and cancer. However, the underlying genomic mechanisms that explain the geographic and carcinogenic diversity of HPV58 variants are still poorly understood. In this study, we used a combination of phylogenetic analyses and bioinformatics to investigate the deep evolutionary history of HPV58 complete genome variants. The initial splitting of HPV58 variants was estimated to occur 478,600 years ago (95% highest posterior density [HPD], 391,000 to 569,600 years ago). This divergence time is well within the era of speciation between Homo sapiens and Neanderthals/Denisovans and around three times longer than the modern Homo sapiens divergence times. The expansion of present-day variants in Eurasia could be the consequence of viral transmission from Neanderthals/Denisovans to non-African modern human populations through gene flow. A whole-genome sequence signature analysis identified 3 amino acid changes, 16 synonymous nucleotide changes, and a 12-bp insertion strongly associated with the E7 T20I/G63S variant that represents the A3 sublineage and carries higher carcinogenetic potential. Compared with the capsid proteins, the oncogenes E7 and E6 had increased substitution rates indicative of higher selection pressure. These data provide a comprehensive evolutionary history and genomic basis of HPV58 variants to assist further investigation of carcinogenic association and the development of diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Human papillomavirus type 16 (HPV16) is the primary etiological agent of cervical cancer, the second most common cancer in women worldwide. Complete genomes of 12 isolates representing the major lineages of HPV16 were cloned and sequenced from cervicovaginal cells. The sequence variations within the open reading frames (ORFs) and noncoding regions were identified and compared with the HPV16R reference sequence (50). This whole-genome approach gives us unprecedented precision in detailing sequence-level changes that are under selection on a whole-viral-genome scale. Of 7,908 base pair nucleotide positions, 313 (4.0%) were variable. Within the 2,452 amino acids (aa) comprising 80RFs, 243 (9.9%) amino acid positions were variable. In order to investigate the molecular evolution of HPV16 variants, maximum likelihood models of codon substitution were used to identify lineages and amino acid sites under selective pressure. Five codon sites in the E5 (aa 48, 65) and E6 (aa 10, 14, 83) ORFs were demonstrated to be under diversifying selective pressure. The E5 ORF had the overall highest nonsynonymous/synonymous substitution rate (ω ) ratio (M3 = 0.7965). The E2 gene had the next-highest to ratio (M3 = 0.5611); however, no specific codons were under positive selection. These data indicate that the E6 and E5 ORFs are evolving under positive Darwinian selection and have done so in a relatively short time period. Whether response to selective pressure upon the E5 and E6 ORFs contributes to the biological success of HPV16, its specific biological niche, and/or its oncogenic potential remains to be established. [ABSTRACT FROM AUTHOR]

Reports on the identification of a locus of seven genes required for nonspecific adherence of Actinobacillus actinomycetemcomitans, a gram-negative bacterium, to surfaces. Isolation of adherence-defective mutants by transposon mutagenesis; Identification of seven tad genes; Tad proteins in fibril secretion system.

Aggregatibacter actinomycetemcomitans is implicated in localized aggressive periodontitis. We report the first genome sequence of an A. actinomycetemcomitans strain isolated from an Old World primate. [ABSTRACT FROM AUTHOR]