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PubMed1998

Identification and characterization of the PutP proline permease that contributes to in vivo survival of Staphylococcus aureus in animal models.

Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscesses, endocarditis, and other infectious syndromes. A signature-tagged mutagenesis (STM) system was adapted for use in studying the genes required for in vivo survival of S. aureus. An STM library was ultimately created in S. aureus RN6390, with Tn917 being used to create the transposon mutations. Pools of S. aureus RN6390 mutants were screened in mouse abscess, bacteremia, and wound infection models for growth attenuation after in vivo passage. One of the mutants that was identified displayed marked attenuation following large-pool screening in all three animal models, which was confirmed in bacteremia and endocarditis models of infection with a smaller pool of mutants. Sequence analysis of the entire open reading frame showed a 99% identity to the high-affinity proline permease (putP) gene characterized in another strain of S. aureus. In wound and murine abscess infection models, the putP mutant was approximately 10-fold more attenuated than was wild-type strain RN6390. Another S. aureus strain transduced with the putP mutation also displayed an attenuated phenotype after passage in the wound model. A [3H]proline uptake assay showed that less proline was specifically transported into the putP mutant than into strain RN6390. The reduced viability of the bacteria possessing the mutation in the S. aureus high-affinity proline permease suggests that proline scavenging by the bacteria is important for in vivo growth and proliferation and that analogs of proline may serve as potential antistaphylococcal therapeutic agents.

Amino Acid Transport Systems, Neutral↗
PubMed2005

Allele frequency distribution under recurrent selective sweeps.

The allele frequency of a neutral variant in a population is pushed either upward or downward by directional selection on a linked beneficial mutation ("selective sweeps"). DNA sequences sampled after the fixation of the beneficial allele thus contain an excess of rare neutral alleles. This study investigates the allele frequency distribution under selective sweep models using analytic approximation and simulation. First, given a single selective sweep at a fixed time, I derive an expression for the sampling probabilities of neutral mutants. This solution can be used to estimate the time of the fixation of a beneficial allele from sequence data. Next, I obtain an approximation to mean allele frequencies under recurrent selective sweeps. Under recurrent sweeps, the frequency spectrum is skewed toward rare alleles. However, the excess of high-frequency derived alleles, previously shown to be a signature of single selective sweeps, disappears with recurrent sweeps. It is shown that, using this approximation and multilocus polymorphism data, genomewide parameters of directional selection can be estimated.

Biological Evolution↗
PubMed2005

Crossed-coil detection of two-photon excited nuclear quadrupole resonance.

Applying a recently developed theoretical framework for determining two-photon excitation Hamiltonians using average Hamiltonian theory, we calculate the excitation produced by half-resonant irradiation of the pure quadrupole resonance of a spin-3/2 system. This formalism provides expressions for the single-quantum and double-quantum mutation frequencies as well as the Bloch-Siegert shift. The dependence of the excitation strength on RF field orientation and the appearance of the free-induction signal along an axis perpendicular to the excitation field provide an unmistakable signature of two-photon excitation. We demonstrate single- and double-quantum excitation in an axially symmetric system using 35Cl in a single crystal of potassium chlorate (omega(Q) = 28 MHz) with crossed-coil detection. A rotation plot verifies the orientation dependence of the two-photon excitation, and double-quantum coherences are observed directly with the application of a static external magnetic field.

Journal Article↗
PubMed1999

The structure of the bovine protein tyrosine phosphatase dimer reveals a potential self-regulation mechanism.

The bovine protein tyrosine phosphatase (BPTP) is a member of the class of low-molecular weight protein tyrosine phosphatases (PTPases) found to be ubiquitous in mammalian cells. The catalytic site of BPTP contains a CX(5)R(S/T) phosphate-binding motif or P-loop (residues 12-19) which is the signature sequence for all PTPases. Ser19, the final residue of the P-loop motif, interacts with the catalytic Cys12 and participates in stabilizing the conformation of the active site through interactions with Asn15, also in the P-loop. Mutations at Ser19 result in an enzyme with altered kinetic properties with changes in the pK(a) of the neighboring His72. The X-ray structure of the S19A mutant enzyme shows that the general conformation of the P-loop is preserved. However, changes in the loop containing His72 result in a displacement of the His72 side chain that may explain the shift in the pK(a). In addition, it was found that in the crystal, the protein forms a dimer in which Tyr131 and Tyr132 from one monomer insert into the active site of the other monomer, suggesting a dual-tyrosine motif on target sites for this enzyme. Since the activity of this PTPase is reportedly regulated by phosphorylation at Tyr131 and Tyr132, the structure of this dimer may provide a model of a self-regulation mechanism for the low-molecular weight PTPases.

Animals↗
PubMed1996

Molecular characterization of a major serotype M49 group A streptococcal DNase gene (sdaD).

Group A streptococci (GAS) express up to four types of secreted DNases. Although GAS infections are correlated with the production of anti-DNase B antibodies, the roles of DNases in the pathogenesis of GAS infections remain unclear. From a lambda library of serotype M49 strain CS101 GAS genome, a 2,147-bp fragment expressing DNase activity on an indicator agar was identified and sequenced. One 1,155-bp open reading frame (ORF) was identified in this fragment. This ORF was found to be 48% identical on the amino acid level to group C streptococcal DNase (Sdc). The regions of highest homology corresponded to amino acid residues that were also identified as part of the active site in staphylococcal nuclease. Transcription analysis revealed a specific 1.3-kb mRNA, which corresponded to the size predicted by the promoter and transcription termination signature sequences and indicated a monocistronic mode of transcription. Allelic replacement of the ORF rendered a M49 mutant devoid of extracellular DNase activity when cultured on indicator agar. Virulence parameters such as resistance to phagocytosis were not affected by the mutation. The sda gene was cloned and expressed in Escherichia coli as a thioredoxin fusion. By performing Ouchterlony immunodiffusion on the recombinant protein and by using protein preparations from culture supernatants of wild-type bacteria and the DNase mutant, the results of immunoreactivity with DNase type-specific polyclonal rabbit antisera classified the DNase as a type D enzyme. Fifty percent of patients with sera exhibiting high titers of antistreptolysin or anti-DNase B antibodies also had SdaD-reactive antibodies in comparison with <10% of serologically normal controls. While the value of recombinant SdaD for diagnostic purposes needs to be clarified, the isogenic DNase mutant pair of M49 should allow the significance of GAS DNase D as a bacterial virulence factor to be determined.

Amino Acid Sequence↗
PubMed2006

Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III.

The cytochrome bc1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr132 and Glu272, and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe129 and Tyr279. Substitution of Phe129 by lysine or arginine yielded a respiration-deficient phenotype and lipid-dependent catalytic activity. Increased bypass reactions were detectable for both variants, with F129K showing the more severe effects. Substitution with lysine leads to a disturbed coordination of a b heme as deduced from changes in the midpoint potential and the EPR signature. Removal of the aromatic side chain in position Tyr279 lowers the catalytic activity accompanied by a low level of bypass reactions. Pre-steady-state kinetics of the enzymes modified at Glu272 and Tyr132 confirmed the importance of their functional groups for electron transfer. Altered center N kinetics and activation of ubiquinol oxidation by binding of cytochrome c in the Y132F and E272D enzymes indicate long range effects of these mutations.

Aspartic Acid↗
PubMed2003

Features of evolution and expansion of modern humans, inferred from genomewide microsatellite markers.

We study data on variation in 52 worldwide populations at 377 autosomal short tandem repeat loci, to infer a demographic history of human populations. Variation at di-, tri-, and tetranucleotide repeat loci is distributed differently, although each class of markers exhibits a decrease of within-population genetic variation in the following order: sub-Saharan Africa, Eurasia, East Asia, Oceania, and America. There is a similar decrease in the frequency of private alleles. With multidimensional scaling, populations belonging to the same major geographic region cluster together, and some regions permit a finer resolution of populations. When a stepwise mutation model is used, a population tree based on TD estimates of divergence time suggests that the branches leading to the present sub-Saharan African populations of hunter-gatherers were the first to diverge from a common ancestral population (approximately 71-142 thousand years ago). The branches corresponding to sub-Saharan African farming populations and those that left Africa diverge next, with subsequent splits of branches for Eurasia, Oceania, East Asia, and America. African hunter-gatherer populations and populations of Oceania and America exhibit no statistically significant signature of growth. The features of population subdivision and growth are discussed in the context of the ancient expansion of modern humans.

Africa↗
PubMed1998

Resonance raman characterization of reaction centers with an Asp residue near the photoactive bacteriopheophytin.

Qy-excitation resonance Raman (RR) studies are reported for a series of Rhodobacter capsulatus reaction centers (RCs) containing mutations at L-polypeptide residue 121 near the photoactive bacteriopheophytin (BPhL). The studies focus on the electronic/structural perturbations of BPhL induced by replacing the native Phe with an Asp residue. Earlier work has shown that the electron-transfer properties of F(L121)D RCs are closely related to those of RCs in which BPhL is replaced by bacteriochlorophyll (BChl) (beta-type RCs) or by pheophytin. In addition to the F(L121)D single mutant, RR studies were performed on the F(L121)D/E(L104)L double mutant, which additionally removes the hydrogen bond between BPhL and the native Glu L104 residue. The vibrational signatures of BPhL in the single and double mutants containing Asp L121 are compared with one another and with those of BPhL in both wild-type and F(L121)L RCs. The replacement of the aromatic Phe residue with Leu has no discernible effect on the vibrational properties of BPhL, a finding in concert with the previously reported absence of an effect of the mutation on the electron-transfer characteristics of the RC. In contrast, replacement of Phe with Asp significantly perturbs the vibrational characteristics of BPhL, and in a manner most consistent with Asp L121 being deprotonated and negatively charged. The negative charge of the carboxyl group of Asp L121 interacts with the pi-electron system of BPhL in a relatively nonspecific fashion, diminishing the contribution of charge-separated resonance forms of the C9-keto group to the electronic structure of the cofactor. The presence of a negative charge near BPhL is consistent with the known photochemistry of F(L121)D RCs, which indicates that the free energy of P+BPhL- is substantially higher than in wild-type RCs.

Aspartic Acid↗
PubMed2026

Characterizing the Discordance between AT-Rich Interacting Domain 1A Protein and Genotype in Endometrioid-Type Endometrial Tumors.

ARID1A is one of the most frequently mutated genes in endometrial cancer, with approximately 40% of patients harboring an ARID1A mutation. However, relatively little is known about how AT-rich interacting domain 1A (ARID1A) protein loss shapes endometrial cancer pathogenesis. Mounting evidence from other malignancies suggests that ARID1A protein can be regulated post-translationally, independent of genotype. However, most studies in endometrial cancer evaluate genotype alone, overlooking the potential for alternative mechanisms of ARID1A loss. To address this gap, ARID1A protein expression and genotype were examined in endometrioid tumors, and associated transcriptional changes were characterized. Evaluation of ARID1A protein in 71 human endometrioid tumors demonstrates that protein loss can occur regardless of ARID1A genotype. Retention or deficiency of ARID1A protein was not significantly related to variant allele frequency or location of mutation in human tumors with mutant ARID1A. A human endometrial cancer cell model suggests that ARID1A protein loss can occur through proteasomal degradation. Furthermore, ARID1A protein expression was found to be a predictor of worse overall survival in The Cancer Genome Atlas cohort of ARID1A wild-type endometrioid tumors. Spatial transcriptomics of 16 human endometrioid tumors revealed that both genotype and protein expression of ARID1A play a role in shaping unique transcriptional signatures in endometrial cancer and can be used to predict patient prognosis. Suggesting evaluation of ARID1A should not be done solely by sequencing techniques.

Humans↗
PubMed2003

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation.

Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves. Both the BK B2 receptor modification and BK-mediated tau Ser phosphorylation are dependent on activation of protein kinase C and can be detected in fibroblasts from persons with Trisomy 21 two decades before the characteristic onset of AD. This dysregulated signaling cascade in AD may thus be expressed throughout life as an aberrant pathway in peripheral tissues more accessible than brain for molecular analysis. The sites of greatest BK B2 receptor expression in brain overlap with those areas displaying the earliest pathology in the course of AD, suggesting that BK receptor pathway dysfunction may be a molecular signature yielding information about the pathogenesis of AD.

Adult↗
PubMed2006

The basal phenotype of BRCA1-related breast cancer: past, present and future.

Many BRCA1-related tumors have a distinct histological characteristics which together have been called "basal-like." Typically such tumors are ER-, HER2- and express cytokeratin 5/6, cytokeratin 8/18, EGFR and vimentin. These characteristics can be used to predict which breast cancers are most likely to be associated with germline BRCA1 mutations which has important implications for breast pathologists. Moreover, BRCA1-related breast cancers generally have a poorer prognosis which may paradoxically be more pronounced in node negative cancers. This may relate in part to a different pattern of metastatic spread with in increased frequency of brain and lung metastases in BRCA1 carriers. Conversely, BRCA1-related tumors may respond better to neoadjuvant chemotherapy and their characteristic molecular signature may provide opportunities to develop specific molecular targeted therapies akin to traztuzumab in HER2+ cancers. Finally, many of the phenotypic features of BRCA1-related tumors might also be found in putative breast stem cells and therefore characterization of the BRCA1 breast cancer phenotype will improve our understanding of sporadic breast carcinogenesis.

Biomarkers, Tumor↗
PubMed2005

[Molecular biology in clinical cancer research: the example of digestive cancers].

Cancer is a DNA disease characterized by uncontrolled cell proliferation due to the accumulation of genetic alterations. Recent progress in molecular biology allowed the identification of markers potentially usefull for patients management through the identification of these genetic alterations and a best understanding of chemotherapy molecular targets. Several examples in digestive oncology underline the relevance of molecular biology in clinical research. If almost all colorectal cancers (CRC) correspond to the same histopathological type (adenocarcinoma), molecular biology allowed the identification of two different molecular mechanisms of colorectal carcinogenesis: chromosomal instability characterized by recurrent allelic losses on chromosomes 17, 5, 18, 8 and 22 that contribute to the inactivation of tumor suppressor genes, and genetic instability characterized by the instability of microsatellite loci due to an alteration of DNA mismatch repair leading to the accumulation of mutations in genes involved in the control of cell cycle and apoptosis. These data are potentially interesting for the management of CRC patients. Indeed, microsatellite instability seems not only to be a good prognostic factor but also a molecular factor that can predict response to adjuvant 5-fluorouracil based chemotherapy. Therapeutic clinical trials taking into account these molecular parameters are still going on. DNA microarray-based gene expression profiling technology that allows the simultaneous analysis of thousand of tumor genes represents also an interesting approach in oncology with the recent identification of a "genetic signature" as a risk factor of tumor recurrence in stage II CRC, a setting in which the benefit of adjuvant chemotherapy remains on debate. At last, a best understanding of chemotherapy molecular targets allowed the identification of genetic markers that can predict the response and/or the toxicity of anti-cancer drugs used in gastrointestinal cancers, which could be helpful in the future to propose for each patient a personalized treatment. Mutations that can predict the response of new target therapies such as the inhibitors of the c-KIT tyrosine kinase activity in gastrointestinal stromal tumors have also been found and will allow the selection of patients who can have benefit from these new therapeutic drugs.

Adenocarcinoma↗
PubMed2005

Mechanism of DNA binding and localized strand separation by Pur alpha and comparison with Pur family member, Pur beta.

Pur alpha is a single-stranded (ss) DNA- and RNA-binding protein with three conserved signature repeats that have a specific affinity for guanosine-rich motifs. Pur alpha unwinds a double-stranded oligonucleotide containing purine-rich repeats by maintaining contact with the purine-rich strand and displacing the pyrimidine-rich strand. Mutational analysis indicates that arginine and aromatic residues in the repeat region of Pur alpha are essential for both ss- and duplex DNA binding. Pur alpha binds either linearized or supercoiled plasmid DNA, generating a series of regularly spaced bands in agarose gels. This series is likely due to localized unwinding by quanta of Pur alpha since removal of Pur alpha in the gel eliminates the series and since Pur alpha binding increases the sensitivity of plasmids to reaction with potassium permanganate, a reaction specific for unwound regions. Pur alpha binding to linear duplex DNA creates binding sites for the phage T4 gp32 protein, an ss-DNA binding protein that does not itself bind linearized DNA. In contrast, Pur beta lacking the Pur alpha C-terminal region binds supercoiled DNA but not linearized DNA. Similarly, a C-terminal deletion of Pur alpha can bind supercoiled pMYC7 plasmid, but cannot bind the same linear duplex DNA segment. Therefore, access to linear DNA initially requires C-terminal sequences of Pur alpha.

Amino Acid Sequence↗
PubMed2025

Cholesterol Metabolism-related Characteristics Predict Therapeutic Response and Survival in Esophageal Cancer.

INTRODUCTION: Cholesterol homeostasis has been identified as an essential downstream pathway of mutations in TP53. Esophageal cancer is one of the most prevalent malignancies exhibiting the mutation. OBJECTIVES: To explore the significance of cholesterol metabolism-related characteristics in tumor phenotype and treatment outcomes of esophageal cancer. METHODS: We established a cholesterol metabolism-related gene set (CMGs) and performed Lasso-Cox analysis to identify prognostic signatures. Nomogram-based risk scores and clinical stages afterwards were constructed and evaluated. We simultaneously identified two metabolic subtypes based on the distinct features of the CMGs. We annotated the functional and pathway characteristics of differentially expressed genes between the clusters and compared the differences in clinical and immune characteristics. Finally, we assessed the prognostic value of signatures in the GSE53625 and two clinical cohorts using whole-exon sequencing and multiplex immunofluorescence. RESULTS: Our study identified five cholesterol prognosis-related genes (CRGs) that demonstrated superior prognostic efficacy in the training set compared to clinical staging, validated in independent public databases and two clinical cohorts. According to the different expression patterns of the signatures, patients were divided into two subtypes. The C1 group demonstrated poorer overall survival, response to immunotherapy, and downregulation of the p53 pathway. In the immune correlation analysis, we found that the risk score based on 5-signature model was significantly positively correlated with the abundance of suppressive immune cells and the immune checkpoints. Finally, we explored the impact of expression and genomic polymorphism of the signatures on the prognosis at the pan-cancer level. CONCLUSIONS: Our findings underscore the distinct expression patterns of CRGs in esophageal cancer. These signatures are efficient to serve as prognostic indicators and assess the effectiveness of immunotherapy. They may also represent promising targets in other TP53 mutant malignancies.

Humans↗
PubMed2024

TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells promoting ACE2-mediated entry with and without TMPRSS2 coexpression. Electron microscopy and inhibitor experiments indicated TMPRSS2-mediated cell entry was associated with increased virion internalization into endosomes, and partially dependent upon clathrin-mediated endocytosis. TMPRSS2 increased panvariant uptake efficiency and enhanced early rates of virus replication, transcription, and secretion, with variant-specific profiles observed. On the host side, transcriptional profiling confirmed the magnitude of infection-induced antiviral and proinflammatory responses were linked to uptake efficiency, with TMPRSS2-assisted entry boosting early antiviral responses. In addition, TMPRSS2-enhanced infections increased rates of cytopathology, apoptosis, and necrosis and modulated virus secretion kinetics in a variant-specific manner. On the virus side, convergent signatures of cell-uptake-dependent innate immune induction were recorded in viral genomes, manifesting as switches in dominant coupled Nsp3 residues whose frequencies were correlated to the magnitude of the cellular response to infection. Experimentally, we demonstrated that selected Nsp3 mutations conferred enhanced interferon antagonism. More broadly, we show that TMPRSS2 orthologues from evolutionarily diverse mammals facilitate panvariant enhancement of cell uptake. In summary, our study uncovers previously unreported associations, linking cell entry efficiency to innate immune activation kinetics, cell death rates, virus secretion dynamics, and convergent selection of viral mutations. These data expand our understanding of TMPRSS2's role in the SARS-CoV-2 life cycle and confirm its broader significance in zoonotic reservoirs and animal models.

SARS-CoV-2↗
PubMed2025

Construction and accuracy assessment of an efferocytosis-related prognostic model for ovarian cancer: A diagnostic accuracy study.

The study aimed to investigate the prognostic significance of efferocytosis-related genes in ovarian cancer (OC) with regard to cancer development, progression, invasion, and metastasis. OC cohorts were assembled from bioinformatics repositories. Utilizing consensus clustering analysis, distinct clusters were delineated based on the intersection of OC-related genes and efferocytosis-related genes. A prognostic signature specific to efferocytosis in OC was developed using data from The Cancer Genome Atlas, validated against the gene expression omnibus database, and subjected to independent prognostic analysis. Subsequently, a nomogram model was formulated. Moreover, investigations encompassed the immune microenvironment, immunotherapy, mutation profiling, drug sensitivity assessments, drug prediction models, and molecular docking analyses. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were employed to ascertain the mRNA expression levels of key genes. Five key genes, FCGBP, BTN3A3, WDR91, SLC25A45, and BTNL3, were identified as significantly associated with OC. Both datasets and qRT-PCR demonstrated elevated expression levels of FCGBP and WDR91 in OC. Notably, AFLATOXIN B1 exhibited strong binding affinity to SLC25A45, ciclopirox to BTN3A3, and irinotecan to WDR91. The risk score, age, and stage were identified as independent prognostic factors, with the nomogram displaying efficacy in predicting OC patient survival. Variations in the immune cell infiltration profiles, including naive B cells, and expression levels of 6 immune checkpoint genes, such as CTLA4, were notable. High tumor mutation burden scores were associated with improved survival outcomes. Additionally, significant differences in the IC50 values of 123 anticancer drugs were observed between the 2 risk groups. This findings of this study highlight the efficacy of the efferocytosis-associated risk model in predicting the survival outcomes of OC patients, thus providing a novel reference for prognostic prediction in OC patients.

Humans↗
PubMed2004

Geographically and temporally distant natural recombinant isolates of Plum pox virus (PPV) are genetically very similar and form a unique PPV subgroup.

Natural recombinant Plum pox virus (PPV) isolates were detected in Albania, Bulgaria, Czech Republic, Germany, Hungary and Slovakia. Despite different geographical origins and dates of isolation, all the recombinant isolates were closely related at the molecular level and shared the same recombination breakpoint as well as a typical signature in their N-terminal coat protein sequence, suggesting a common origin. Biological assays with four recombinant isolates demonstrated their capacity to be aphid-transmitted to various Prunus hosts. One of these isolates had a threonine-to-isoleucine mutation in the conserved PTK motif of its HC-Pro and showed a drastically decreased, although not abolished, aphid transmissibility. The complete genome sequence of one of the recombinant isolates, BOR-3, was determined, as well as some partial sequences in the HC-Pro and P3 genes for additional natural recombinant isolates. Analysis of the phylogenetic relationships between the recombinant isolates and other sequenced PPV isolates confirmed that the recombinant isolates form a phylogenetically homogeneous lineage. In addition, this analysis revealed an ancient recombination event between the PPV-D and M subgroups, with a recombination breakpoint located in the P3 gene. Taken together, these results indicate that recombinant isolates represent an evolutionarily successful, homogeneous group of isolates with a common history and unique founding recombination event. The name PPV-Rec is proposed for this coherent ensemble of isolates.

Animals↗