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Biomedical subjects

K O'Donnell

Publications and source records attributed to K O'Donnell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams.

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1999

Expression of receptor tyrosine kinase Axl and its ligand Gas6 in rheumatoid arthritis: evidence for a novel endothelial cell survival pathway.

Angiogenesis and synovial cell hyperplasia are characteristic features of rheumatoid arthritis (RA). Many growth and survival factors use receptors belonging to the tyrosine kinase family that share conserved motifs within the intracellular catalytic domains. To understand further the molecular basis of cellular hyperplasia in RA, we have used degenerate primers based on these motifs and RNA obtained from the synovium of a patient with RA to perform reverse transcriptase-polymerase chain reaction. We report detection of the receptor tyrosine kinase (RTK) Axl in RA synovium and we document the expression pattern of Axl in capillary endothelium, in vascular smooth muscle cells of arterioles and veins, and in a subset of synovial cells in RA synovial tissue. Gas6 (for growth arrest-specific gene 6), which is a ligand for Axl and is related to the coagulation factor protein S, was found in synovial fluid and tissue from patients with RA and osteoarthritis. Axl expression and function was studied in human umbilical vein endothelial cells (HUVECs). Gas6 bound to HUVECs; soluble Axl inhibited this binding. Exogenous Gas6 protected HUVECs from apoptosis in response to growth factor withdrawal and from TNFalpha-mediated cytotoxicity. These findings may reveal a new aspect of vascular physiology, which may also be relevant to formation and maintenance of the abnormal vasculature in the rheumatoid synovium.

Arthritis, Rheumatoid↗
PubMed1999

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation.

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Antiviral Agents↗
PubMed1999

Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function.

CASE REPORT: A patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining. CONCLUSION: Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.

Aged↗
PubMed1999

Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Adolescent↗
PubMed1998

Identification of a truncated form of the CC chemokine CK beta-8 demonstrating greatly enhanced biological activity.

A new CC chemokine, designated CKbeta-8 or myeloid progenitor inhibitor factor-1, was recently identified in a large scale sequencing effort and was cloned from a human aortic endothelial library. CKbeta-8 cDNA encodes a signal sequence of 21 amino acids, followed by a 99-amino acid predicted mature form. CKbeta-8 was expressed and purified from a baculovirus insect cell expression system, which resulted in the identification of different N-terminal variants of the secreted chemokine. The three major forms (containing amino acids 1-99, 24-99, and 25-99 of the secreted chemokine) showed a large variation in potency. CKbeta-8 activated both monocytes and eosinophils to mobilize intracellular calcium; however, the shortest form of CKbeta-8 (25-99) was >2 orders of magnitude more potent than the longest form. Cross-desensitization experiments in both monocytes and eosinophils suggested that the CCR1 receptor was probably the predominant receptor that mediates this chemokine's physiologic response. However, incomplete desensitization was encountered in both cell systems, suggesting involvement of an additional receptor(s). Interestingly, the short form of CKbeta-8 was the most potent chemotactic chemokine that we have ever evaluated in the monocyte system (EC50 = 54 pM). However, in contrast to its action on monocytes, CKbeta-8 was a very poor chemotactic factor for eosinophils.

Amino Acid Sequence↗
PubMed1998

Site-directed mutagenesis probing the catalytic role of arginines 165 and 166 of human cytomegalovirus protease.

Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and Epstein-Barr virus (EBV). Each member of this family encodes a serine protease that is a potential target for antiviral therapeutic intervention. We recently reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella, A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid, S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165 and Arg166 residues are involved in stabilizing the oxyanion intermediate in human herpes protease catalyzed reactions through the backbone NH and side chain, respectively. In the current study, site-directed mutagenesis was carried out to probe the catalytic function of these two amino acid residues. Substitution of Arg166 with an alanine has led to ablation of enzymatic activity without detectable change in CMV protease conformation, supporting suggestions from the crystal structure that Arg166 side chain plays a major role in catalysis. The wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was shown previously to hold a water molecule that can act as a hydrogen-bond donor to the oxyanion and was thus proposed to stabilize the oxyanion intermediate. However, kinetic characterization of the mutant R165A only reveals a 2.7-fold lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/- 0.4 min-1. These results confirm that Arg165 side chain is not involved in the stabilization of the oxyanion. It is likely that Arg165 only utilizes the backbone NH for catalysis as suggested by the crystal structure.

Alanine↗
PubMed1998

Multiple evolutionary origins of the fungus causing Panama disease of banana: concordant evidence from nuclear and mitochondrial gene genealogies.

Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture. Previous work has indicated that F. oxysporum f. sp. cubense consists of several clonal lineages that may be genetically distant. In this study we tested whether lineages of the Panama disease pathogen have a monophyletic origin by comparing DNA sequences of nuclear and mitochondrial genes. DNA sequences were obtained for translation elongation factor 1alpha and the mitochondrial small subunit ribosomal RNA genes for F. oxysporum strains from banana, pathogenic strains from other hosts and putatively nonpathogenic isolates of F. oxysporum. Cladograms for the two genes were highly concordant and a partition-homogeneity test indicated the two datasets could be combined. The tree inferred from the combined dataset resolved five lineages corresponding to "F. oxysporum f. sp. cubense" with a large dichotomy between two taxa represented by strains most commonly isolated from bananas with Panama disease. The results also demonstrate that the latter two taxa have significantly different chromosome numbers. F. oxysporum isolates collected as nonpathogenic or pathogenic to other hosts that have very similar or identical elongation factor 1alpha and mitochondrial small subunit genotypes as banana pathogens were shown to cause little or no disease on banana. Taken together, these results indicate Panama disease of banana is caused by fungi with independent evolutionary origins.

Base Sequence↗
PubMed1998

Molecular phylogenetic, morphological, and mycotoxin data support reidentification of the Quorn mycoprotein fungus as Fusarium venenatum.

Molecular phylogenetic, morphological, and mycotoxin data were obtained in order to investigate the relationships and identity of the Quorn mycoprotein fungus within Fusarium and to examine Quorn strains and commercial Quorn food products for trichothecene mycotoxins. Phylogenetic analyses of aligned DNA sequences obtained via the polymerase chain reaction from the nuclear 28S ribosomal DNA, nuclear ribosomal internal transcribed spacer region, and beta-tubulin gene exons and introns indicate that the Quorn fungus is Fusarium venenatum, rather than F. graminearum as previously reported. All of the Quorn strains examined were morphologically degenerate aconidial colonial mutants except for NRRL 25139, which produced chlamydospores in recurved terminal chains together with mostly 5-septate sporodochial conidia on doliform monophialides diagnostic of F. venenatum. Bootstrap and decay analyses provide strong support for a monophyletic lineage containing F. venenatum and several other type A trichothecene-producing species, while reference strains of F. graminearum were nested in a separate clade of species that produce type B trichothecenes and/or zearalenone. Analysis of mycotoxins from rice cultures inoculated with Quorn strain NRRL 25416 revealed that four type A trichothecenes are produced, but at low levels relative to strain NRRL 22198 of F. venenatum. No trichothecene mycotoxins, however, were detected from the analysis of three commercial Quorn products marketed for human consumption in England.

DNA, Fungal↗
PubMed1997

Active site cavity of herpesvirus proteases revealed by the crystal structure of herpes simplex virus protease/inhibitor complex.

Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for herpes labialis (cold sores) and genital herpes, respectively. They encode a serine protease that is required for viral replication, and represent a viable target for therapeutic intervention. Here, we report the crystal structures of HSV-1 and HSV-2 proteases, the latter in the presence and absence of the covalently bound transition state analog inhibitor diisopropyl phosphate (DIP). The HSV-1 and HSV-2 protease structures show a fold that is neither like chymotrypsin nor like subtilisin, and has been seen only in the recently determined cytomegalovirus (CMV) and varicella-zoster virus (VZV) protease structures. HSV-1 and HSV-2 proteases share high sequence homology and have almost identical three-dimensional structures. However, structural differences are observed with the less homologous CMV protease, offering a structural basis for herpes virus protease ligand specificity. The bound inhibitor identifies the oxyanion hole of these enzymes and defines the active site cavity.

Binding Sites↗
PubMed1997

Cloning, in vitro expression, and functional characterization of a novel human CC chemokine of the monocyte chemotactic protein (MCP) family (MCP-4) that binds and signals through the CC chemokine receptor 2B.

Here we describe the characterization of a novel human CC chemokine, tentatively named monocyte chemotactic protein (MCP-4). This chemokine was detected by random sequencing of expressed sequence tags in cDNA libraries. The full-length cDNA revealed an open reading frame for a 98-amino acid residue protein, and a sequence alignment with known CC chemokines showed high levels of similarity (59-62%) with MCP-1, MCP-3, and eotaxin. MCP-4 cDNA was cloned into Drosophila S2 cells, and the mature protein (residues 24-98) was purified from the conditioned medium. Recombinant MCP-4 induced a potent chemotactic response (EC50 = 2.88 +/- 0.15 nM) and a transient rise in cytosolic calcium concentration in fresh human peripheral blood monocytes but not in neutrophils. Binding studies in monocytes showed that MCP-4 and MCP-3 were very potent in displacing high affinity binding of 125I-MCP-1 (IC50 for MCP-4, MCP-3, and unlabeled MCP-1 of 2.1 +/- 1.4, 0.85-1.6, and 0.7 +/- 0.2 nM respectively), suggesting that all three chemokines interact with the CC chemokine receptor-2 (MCP-1 receptor). This was confirmed in binding studies with Chinese hamster ovary cells, stably transfected with the CC chemokine 2B receptor. Northern blot analysis in extracts of normal human tissues showed expression of mRNA for MCP-4 in small intestine, thymus, and colon, but the level of protein expression was too low to be detected in Western blot analysis. However, expression of MCP-4 protein was demonstrated by immunohistochemistry in human atherosclerotic lesion and found to be associated with endothelial cells and macrophages.

Amino Acid Sequence↗
PubMed1997

Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients.

BACKGROUND: Complications of the biliary anastomosis are the principal cause of clinically serious bacterial sepsis in liver transplant recipients. Reported series suggest an association of bacterial and fungal infection with cytomegalovirus (CMV) infection, although the mechanism of this association is unclear. METHODS: We examined the association of serious bacterial sepsis with CMV replication in a cohort of 106 consecutive liver transplant recipients. Sequentially collected buffy coats were examined with a polymerase chain reaction (PCR) assay that has been shown to have good predictive value for the development of CMV infection. For selected patients, CMV-specific IgM response and serum tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ten of 13 patients with serious bacterial sepsis developed buffy coat PCR positivity, compared with 26 of 93 patients without bacterial sepsis (chi-square, P<0.001). Ten of 10 septic recipients with a seropositive liver donor developed PCR positivity. For 9 of 10 recipients, bacterial sepsis developed before PCR positivity. Bacterial sepsis was associated with high serum levels of TNF-alpha. Immune response to CMV (reflected by the appearance CMV-specific IgM) was apparently affected by bacterial sepsis, and IgM response was not observed for the three septic patients who died during the study period. CONCLUSIONS: We conclude that CMV replication is encouraged by serious bacterial sepsis. Replication may be promoted by high antecedent levels of TNF-alpha, and/or by poor immune response to CMV in the context of serious bacterial infection.

Antibodies, Viral↗
PubMed1997

Patterns of viremia in liver transplant recipients with symptomatic cytomegalovirus infection.

Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of clinical symptoms in immunosuppressed patients. We have developed an assay for quantitation of CMV DNA in serum. The assay requires the coamplification by polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of mutated internal standard DNA, and then an ELISA detection system. We examined 133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera were examined by quantitative PCR, and buffy coats were examined by qualitative PCR (with a detection threshold of approximately 40 copies per 150,000 cells). Serum viral titers peaked during the seventh week after transplant (median day 40, range 26-58) at about the time of symptom onset. Mean viral titer measured during the seventh week was 1.2 x 10(5) copies per milliliter of serum (standard error 6.5 x 10(4). Buffy-coat PCR results were generally concordant with results of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as symptoms resolved with reduction of immunosuppression and specific antiviral therapy. High titers and poor response to antiviral therapy were observed in the context of excessive immunosuppression and bacterial sepsis. Measurement of serum CMV titer may be useful for the management of immunosuppressed transplant recipients, and provides a tool for the better understanding of factors that enhance or inhibit viral replication.

Antibodies, Viral↗
PubMed1997

Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils.

Eotaxin has been found to bind exclusively to a single chemokine receptor, CCR3. Using expression sequence tag screening of an activated monocyte library, a second chemokine has been identified; it was expressed and purified from a Drosophila cell culture system and appears to only activate CCR3. Eotaxin-2, MPIF-2, or CKbeta-6, is a human CC chemokine with low amino acid sequence identity to other chemokines. Eotaxin-2 promotes chemotaxis and Ca2+ mobilization in human eosinophils but not in neutrophils or monocytes. Cross-desensitization calcium mobilization experiments using purified eosinophils indicate that eotaxin and MCP-4, but not RANTES, MIP-1alpha, or MCP-3, can completely cross-desensitize the calcium response to eotaxin-2 on these cells, indicating that eotaxin-2 shares the same receptor used by eotaxin and MCP-4. Eotaxin-2 was the most potent eosinophil chemoattractant of all the chemokines tested. Eotaxin-2 also displaced 125I-eotaxin bound to the cloned CCR3 stably expressed in CHO cells (CHO-CCR3) and to freshly isolated human eosinophils with affinities similar to eotaxin and MCP-4. 125I-Eotaxin-2 binds with high affinity to eosinophils and both eotaxin and cold eotaxin-2 displace the ligand with equal affinity. Eotaxin and eotaxin-2 promote a Ca2+ transient in RBL-2H3 cells stably transfected with CCR3 (RBL-2H3-CCR3) and both ligands cross-desensitized the response of the other but not the response to LTD4. The data indicate that eotaxin-2 is a potent eosinophil chemotactic chemokine exerting its activity solely through the CCR3 receptor.

Amino Acid Sequence↗
PubMed1997

Enhanced (cytomegalovirus) viral replication after transplantation for fulminant hepatic failure.

Fulminant hepatic failure (FHF) is an established indication for liver transplantation. A pretransplant diagnosis of FHF may be a risk factor for subsequent development of cytomegalovirus (CMV) infection, although the mechanism of this association is not understood. FHF is associated with very high levels of tumor necrosis factor alpha (TNF-alpha), and TNF-alpha may directly promote viral replication. We have used the polymerase chain reaction (PCR) to examine sequentially collected buffy coats from 106 consecutive adult liver transplant recipients. PCR evidence of CMV replication was found for 13 of 18 patients who underwent transplantation for FHF (c.f. 23/88 non-FHF patients; P < .01). Ten of 12 patients who received transplants transplanted for fulminant seronegative hepatitis were buffy-coat PCR-positive, sometimes during the first posttransplant week. TNF-alpha was measured by enzyme-linked immunosorbent assay in selected sera, and results were examined in the context of a quantitative PCR assay. Serum TNF-alpha levels increased and decreased in concert with viral titers. High levels of TNF-alpha were not found in the early posttransplant period. We conclude that FHF (in particular, seronegative hepatitis) is associated with enhanced CMV replication in the posttransplant period. Results also suggest that viral replication may be enhanced before transplantation. These patients may be at special risk for development of symptomatic CMV infection.

Cytomegalovirus↗
PubMed1997

Two divergent intragenomic rDNA ITS2 types within a monophyletic lineage of the fungus Fusarium are nonorthologous.

The evolutionary history of the phytopathogenic Gibberella fujikuroi complex of Fusarium and related species was investigated by cladistic analysis of DNA sequences obtained from multiple unlinked loci. Gene phylogenies inferred from the mitochondrial small subunit (mtSSU) rDNA, nuclear 28S rDNA, and beta-tubulin gene were generally concordant, providing strong support for a fully resolved phylogeny of all biological and most morphological species. Discordance of the nuclear rDNA internal transcribed spacer 2 (ITS2) gene tree is due to paralogous or xenologous ITS2 sequences. PCR and sequence analysis demonstrated that every strain of the ingroup species tested possesses two highly divergent nonorthologous ITS2 types designated type I and type II. Only the major ITS2 type, however, is discernable when PCR products are amplified and sequenced directly with conserved primers. The minor ITS2 type was recovered using ITS2 type-specific PCR primers. Distribution of the major ITS2 type within the species lineages exhibits a homoplastic pattern of evolution, thus obscuring true phylogenetic relationships. The results suggest that the ancestral ITS2 types may have arisen following an ancient interspecific hybridization or gene duplication which occurred prior to the evolutionary radiation of the Gibberella fujikuroi complex and related species of Fusarium. The results also indicate that current morphological-based taxonomic schemes for these fungi are unnatural and a new classification is required.

Base Sequence↗