Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “conservation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2002

RNA secondary structure and squence conservation in C1 region of human immunodeficiency virus type 1 env gene.

We have analyzed amino acid, nucleotide sequence, and RNA secondary structure variability in the env gene of human immunodeficiency virus type (HIV-1). In applying algorithms for computing optimal RNA-folding patterns to a nonredundant data set of 178 env nucleotide sequences, we found a conserved RNA stem-loop structure in the first conserved (C1) region of the env gene. This detailed examination also revealed the known secondary structure conservation of the Rev-responsive element (RRE). This finding is also supported by a higher third position conservation of the translatable reading frame along these subregions. The typical folding of the C1 region consists of two isolated stem-loop structures. These highly conserved structures are likely to have a biological function. This assumption is supported by the conservation of the third position along the coding region of these structures. The third position retains a conservation level above what would be statistically expected.

Algorithms↗
PubMed1998

Mechanisms of copper conservation in organs.

Organ copper is conserved in response to dietary copper restriction. In organs such as brain and heart, conservation is highly efficient, resulting in the loss of little organ copper. In contrast, conservation of copper in liver is induced only after a significant amount of organ copper is lost. Thus, the conservation of copper during dietary restriction is highly organ specific. Although the long-term pattern of organ copper conservation in rats has now been described through use of the continuous feeding of a single stable isotope, the mechanisms responsible for this conservation have not been identified or studied. These mechanisms may include copper-regulated changes in gene expression as well as other mechanisms. We now have the molecular tools that will permit the isolation of copper-regulated genes that may play a role in the conservation of organ copper. Identification of these mechanisms will allow the exploration of the effects of mild short-term and long-term copper deficiency and the role of copper in other physiologic and biochemical systems.

Animals↗
PubMed1995

Evidence for conservative (two-progeny) DNA double-strand break repair.

The double-strand break repair models for homologous recombination propose that a double-strand break in a duplex DNA segment is repaired by gene conversion copying a homologous DNA segment. This is a type of conservative recombination, or two-progeny recombination, which generates two duplex DNA segments from two duplex DNA segments. Transformation with a plasmid carrying a double-strand gap and an intact homologous DNA segment resulted in products expected from such conservative (two-progeny) repair in Escherichia coli cells with active E. coli RecE pathway (recBC sbcA) or with active bacteriophage lambda Red pathway. Apparently conservative double-strand break repair, however, might result from successive events of nonconservative recombination, or one-progeny recombination, which generates only one recombinant duplex DNA segment from two segments, involving multiple plasmid molecules. Contribution of such intermolecular recombination was evaluated by transformation with a mixture of two isogenic parental plasmids marked with a restriction site polymorphism. Most of the gap repair products were from intramolecular and, therefore, conservative (two-progeny) reaction under the conditions chosen. Most were conservative even in the absence of RecA protein. The double-strand gap repair reaction was not affected by inversion of the unidirectional replication origin on the plasmid. These results demonstrate the presence of the conservative (two-progeny) double-strand break repair mechanism. These experiments do not rule out the occurrence of nonconservative (one-progeny) recombination since we set up experimental conditions that should favor detection of conservative (two-progeny) recombination.

Bacteriophage lambda↗
PubMed2002

Measures of synteny conservation between species pairs.

Measures of conserved synteny are important for estimating the relative rates of chromosomal evolution in various lineages. We present a natural way to view the synteny conservation between two species from an Oxford grid--an r x c table summarizing the number of orthologous genes on each of the chromosomes 1 through r of the first species that are on each of the chromosomes 1 through c of the second species. This viewpoint suggests a natural statistic, which we denote by rho and call syntenic correlation, designed to measure the amount of synteny conservation between two species. This measure allows syntenic conservation to be compared across many pairs of species. We improve the previous methods for estimating the true number of conserved syntenies given the observed number of conserved syntenies by taking into account the dependency of the numbers of orthologues observed in the chromosome pairings between the two species and by determining both point and interval estimators. We also discuss the application of our methods to genomes that contain chromosomes of highly variable lengths and to estimators of the true number of conserved segments between species pairs.

Biological Evolution↗
PubMed1995

Local control following breast-conserving surgery for invasive cancer: results of clinical trials.

Prospective, randomized clinical trials have demonstrated that the alternatives of mastectomy or conservative surgery plus radiation therapy provide equivalent survival for patients with invasive breast cancer. The identification of a subset of women who could undergo conservative surgery without radiotherapy would avoid the costs, inconvenience, and complications of radiotherapy and is an important research goal. Four randomized trials comparing conservative surgery alone with conservative surgery plus radiotherapy have demonstrated an average reduction in the risk of disease recurrence in the breast of 84% with the use of radiotherapy. No significant differences in survival have been observed, although the available studies lack sufficient numbers of patients to demonstrate a potential small, but clinically important, survival advantage for patients treated with radiotherapy. Subset analysis in the randomized trials and prospective studies of highly selected patients have failed to consistently identify a group of patients who do not benefit from radiation therapy. Any recurrence of breast cancer is psychologically devastating, and fewer than one half of the patients who have had disease recurrence after conservative surgery alone have undergone further breast-conserving treatment. At present, a group of patients who do not require radiotherapy has not been reproducibly identified, and radiotherapy should remain a part of breast-conserving therapy for invasive carcinoma.

Breast Neoplasms↗
PubMed2006

Survey of conserved alternative splicing events of mRNAs encoding SR proteins in land plants.

The serine/arginine-rich (SR) protein family plays an important role in constitutive and alternative splicing (AS). These proteins regulate AS in a tissue-specific and stress-responsive manner. Pre-mRNAs encoding SR proteins are often alternatively spliced, and these AS events may be important for the regulation of AS events of other pre-mRNAs. In this study, we analyzed AS events of SR proteins in Arabidopsis thaliana and Oryza sativa (rice). We found three sets of AS events conserved between Arabidopsis and rice. These conserved AS events were found in the plant-novel-SR protein, SC35-like (SCL), and two-Zn-knuckles-type 9G8 subfamilies. Each member of these subfamilies has at least one RNA recognition motif (RRM) and at least one intron in the RRM-encoded region. We found that the conserved AS events occurred in these introns and, in each case, the conserved AS events resulted in mature mRNAs encoding proteins with incomplete RRMs. To search for the evolutionary origin of these AS events, we analyzed SR proteins in Physcomitrella patens (moss) in addition to those in Arabidopsis and rice. We found moss homologues of the plant-novel-SR protein, SCL, and the two-Zn-knuckles-type 9G8 subfamilies in silico, and these homologues have long introns at the same location of the conserved AS sites in Arabidopsis and rice. Such long introns are quite specific for alternatively spliced introns concerning the Arabidopsis SR protein genes. The long introns found in the moss SR protein genes strongly suggested that conserved AS events in moss SR protein genes might be similar to those in Arabidopsis and rice. We traced the evolutionary origin of the conserved AS events to 400 MYA, when plants first invaded land. These events are likely important in the regulation of whole AS events and likely contribute to the complicated transcriptome described by AS. The complicated transcriptome created by regulated AS events might have provided plants tolerance against droughts or temperature shifts and given them the ability to live on land.

Alternative Splicing↗
PubMed2002

Conserved water molecules in MHC class-I molecules and their putative structural and functional roles.

A set of conserved water positions making direct contacts with the alpha1 and alpha2 domains of the MHC class-I protein was identified by a cluster analysis in 12 high-resolution crystal structures of proteins from different allele types and different species, comprising human, mouse and rat. The analysis revealed a total of 63 clusters, corresponding to water molecules, whose positions are conserved in half or more of the analyzed structures. Analysis of these clusters shows that the most conserved water positions-those appearing in the largest fraction of the structures-were also the most accurately defined, as measured by their normalized crystallographic B-factor. Not too surprisingly, these positions displayed better overlap and formed more H-bonds with the protein. In a second part of this work, a detailed analysis is presented of three of the most conserved water positions and their putative structural and functional roles are discussed. The most highly conserved of the three appears to play an important role in stabilizing the conformation of a twisted beta-turn between residues 118 and 122 (numbering of HLA-B3501, PDB code 1A1N). An equivalent water molecule was found to be associated with a similar beta-turn in 43 unrelated structures surveyed in the PDB, leading to the suggestion that this water molecule plays an important structural role in this type of turn. The second water molecule makes hydrogen bonds with residues lining pocket B in the peptide-binding groove and is suggested to play a role in modulating peptide recognition. The third highly conserved water molecule is located at the first kink of the alpha2 helix, possibly playing a role in determining the position of the N-terminal segment of that helix, which also carries side chains in contact with the bound peptide. This information on conserved water positions in MHC class-I molecules should be helpful in modeling interactions with bound peptide antigens and in designing new peptides with tailor-made affinities.

Animals↗
PubMed2000

Examining the use of breast-conserving treatment for women with breast cancer in a managed care environment.

At a National Institutes of Health Consensus Conference in 1991, conservation treatment was considered preferable for patients with early-stage breast cancer. In the early and mid-1990s, however, less than half of the eligible patients received this treatment and the rates varied with patient and provider characteristics. This study explores whether more eligible patients with breast cancer received conservation treatment in recent years in a managed care environment compared to reports in the literature, and if patient and hospital characteristics affected the rate of acceptance. The study population included 753 women with breast cancer in clinical stages 0, I, or II. Patients with Stage III or IV tumors or with tumors larger that 5.0 cm were excluded. A multiple logistic regression incorporated in a mixed-effect model was used to estimate the effect of patient and facility characteristics on the likelihood of using breast-conserving surgery controlling for clinical stages and demographics such as age, race, and marital status. Among the 753 eligible patients, 474 (62.9%) received conservation surgery. Only Hispanic ethnicity and clinical stage significantly affected the likelihood of receiving conservation treatment. Factors such as patient age, hospital size, and teaching status that had been found to be significant predictors in earlier studies were not statistically significant in this study, although conservation treatment was more frequent in younger women and in teaching hospitals. A larger proportion of eligible patients received conservative treatment in this study than in previous reports. This treatment became available in a broader range of institutions, moving from large, academic teaching centers to smaller community hospitals.

Adult↗
PubMed1996

Breast conservation therapy after augmentation mammaplasty: is it appropriate?

Breast conservation therapy, consisting of lumpectomy, axillary node dissection, whole-breast irradiation, and a boost to the tumor bed, is an increasingly popular option for the treatment of breast cancer. Among patients with stage I and stage II disease, breast conservation therapy yields survival rates equivalent to those for mastectomy. The cosmetic results of radiotherapy are usually good, and this approach preserves an intact, sensate breast. Most studies on breast conservation therapy, however, have been performed in nonaugmented patients. Relatively little has been published regarding breast conservation therapy in the presence of silicone implants. Between 1981 and 1994, we treated 33 augmented patients with breast conservation therapy. Among 26 individuals for whom complete follow-up data were available, 17 (65 percent) developed significant capsular contracture on the irradiated side. Thus far 8 patients with radiation-induced contracture have undergone corrective surgery. In our experience, augmented breast cancer patients treated with breast conservation therapy have less satisfactory cosmetic results than nonaugmented women. In addition, mammographic follow-up, critical for identifying local recurrence, may be impaired by the presence of an implant and capsular contracture. On the basis of these considerations, breast conservation therapy may be less than optimal in augmented cancer patients unless explantation is performed before treatment.

Adult↗
PubMed2000

Increased signal intensity of the spinal cord on magnetic resonance images in cervical compressive myelopathy. Does it predict the outcome of conservative treatment?

STUDY DESIGN: Correlation between a lesion of the spinal cord that elicits increased signal intensity (ISI) on magnetic resonance images (MRIs) and the outcome of conservative treatment for cervical compressive myelopathy was retrospectively investigated. OBJECTIVE: To investigate whether ISI could predict the outcome of conservative treatment for cervical compressive myelopathy. SUMMARY OF BACKGROUND DATA: It is unknown whether ISI is related to the outcome of conservative treatment for cervical compressive myelopathy. METHODS: Fifty-two patients with mild cervical myelopathy underwent conservative treatment with a cervical brace. The compressive lesions were spondylosis in 29 patients, disc herniation in 12, and an ossification of the longitudinal ligament in 11. They also underwent MRI (1.5 T), and ISI was evaluated on T2-weighted sagittal and axial images. The ISI areas were classified as focal or multisegmental. Thirty-nine patients underwent follow-up MRI after a mean interval of 2 years, 4 months. The transverse area of the spinal cord was also measured on T2-weighted axial images. The outcome of conservative treatment was assessed using the Japanese Orthopedic Association Score (JOA score). Patients showing either an improvement in the JOA score or with a JOA score of 15 or more were considered to have a satisfactory outcome. RESULTS: The average JOA score was 14.0 +/- 1.4 (range, 10-16) before conservative treatment and 14.4 +/- 1.9 (range, 10-17) at follow-up. The average gain in the JOA score was 0.4 points +/- 1.9 (range, -5 to +6). The outcome was satisfactory in 36 patients (69%). An area of ISI was observed in 34 patients (65%) before treatment (24 focal and 10 multisegmental). A satisfactory outcome was obtained in 78% of the patients without ISI, in 63% of those with focal ISI, and in 70% of those with multisegmental ISI. No statistically significant difference was seen among these three groups in the percentages of patients with satisfactory outcome, JOA scores before and after treatment or transverse spinal cord area. Of the 39 patients who were re-examined by MRI, 28 showed an area of ISI. The ISI regressed in five patients (18%). Satisfactory outcome was obtained in all 5 patients with regression of ISI, in 16 (70%) of the 23 patients without regression of ISI, and in 10 (91%) of the 11 patients without ISI apparent on the the first images (difference, not significant). CONCLUSIONS: Increased signal intensity was not related to a poor outcome of conservative treatment or severity of myelopathy in the patients with mild cervical myelopathy.

Adult↗
PubMed2002

A comparative analysis of translated dihydropyrimidine dehydrogenase cDNA; conservation of functional domains and relevance to genetic polymorphisms.

A pharmacogenetic syndrome caused by molecular defects in the dihydropyrimidine dehydrogenase gene (DPYD ) results in partial to complete loss of dihydropyrimidine dehydrogenase (DPD) enzyme activity with patients exhibiting life-threatening toxicity following administration of routine doses of 5-fluorouracil. To date, more than 19 reported mutations have been putatively associated with DPD deficiency with 16 occurring within the open reading frame of the cDNA. The purpose of this study was to examine the conservation of functional domains (including the uracil, flavine adenine dinucleotide and NADPH binding sites) across three phyla (Chordata, Arthropoda and Nematoda) and the conservation of regions corresponding to the previously reported mutations. Comparative analysis of the uracil and NADPH binding sites in mammals and invertebrates demonstrated 100% amino acid identity between mammals and Drosophila melanogaster. Caenorhabditis elegans demonstrated 89% and 88% identity in these domains, respectively. The mammalian sequences demonstrated 100% identity in two iron sulphur motifs (amino acids 953-964 and 986-997) with significant conservation in D. melanogaster (92% and 92% identity, respectively) and C. elegans (100% and 92% identity, respectively). Comparative amino acid analysis revealed non-conservation in the loci of four DPYD mutations [DPYD*12 (R21Q), DPYD*5 (I543V), DPYD*6 (V732I), DPYD*9A (C29R)]. Seven mutations occurred in highly conserved regions [M166V, DPYD*8 (R235W), DPYD*11 (V335l), DPYD*4 (S534N), DPYD*9B (R886H), D949V, DPYD*10 (V995F)]. In summary, this comparative analysis identified conserved regions which may be critical to enzyme structure and/or function. The conservation of loci where DPYD mutations occur was also examined to evaluate their functional significance on DPD enzyme activity. These data should prove useful in the evaluation of newly discovered mutations in the DPYD gene.

Amino Acid Sequence↗
PubMed2005

Long-term outcome of conservative treatment in patients with diverticulitis of the sigmoid colon.

INTRODUCTION: The indication for surgery after conservative treatment of acute diverticulitis is still under debate. This is partly as a result of limited data on the outcome of conservative management in the long run. We therefore aimed to determine the long-term results of conservative treatment for acute diverticulitis. METHODS: The records of all patients treated at our institution for diverticulitis between 1985 and 1991 were reviewed (n=363, median age 64 years, range 29-93). Patients who received conservative treatment were interviewed in 1996 and 2002 [follow-up time 7 years 2 months (range 58-127 months) and 13 years 4 months (range 130-196 months). RESULTS: A total of 252 patients (69%) were treated conservatively, whereas 111 (31%) were operated on. At the first follow-up, 85 patients treated conservatively had died, one of them from bleeding diverticula. A recurrence of symptoms was reported by 78 of the remaining 167 patients, and 13 underwent surgery. At the second follow-up, one patient had died from sepsis after perforation during another episode of diverticulitis. Thirty-one of the 85 patients interviewed reported symptoms and 12 had been operated on. In summary, at the second follow-up interview, 34% of patients treated initially had had a recurrence and 10% had undergone surgery. No predictive factors for the recurrence of symptoms or later surgery could be determined. CONCLUSION: Despite a high rate of recurrences after conservative treatment of acute diverticulitis, lethal complications are rare. Surgery should thus mainly be undertaken to achieve relief of symptoms rather than to prevent death from complications.

Acute Disease↗
PubMed2004

Long-term experience with surgical and conservative treatment of penile fracture.

PURPOSE: Immediate surgical repair is widely accepted as the therapy of choice in penile fracture. As recent reports show, good results can also be achieved in some patients with conservative management. It is unclear which patients will truly benefit from an operation. We retrospectively compared the long-term outcomes of surgical and conservative treatment in patients with penile fracture. MATERIALS AND METHODS: In 22 years we treated 29 patients with penile fracture. A total of 12 patients were treated with immediate surgical repair and 17 patients were treated conservatively. Patient charts were reviewed and all patients had followup by interview with an additional clinical evaluation if the result was not completely satisfactory. Outcome was rated good, moderate or poor. RESULTS: Mean followup was 67 months. There was no statistical difference between patients in the surgery group and patients in the conservative group in regard to length of followup, age at presentation or length of hospital stay. In the surgery group and the conservative group 11 (92%) and 10 (59%) patients showed good outcome, respectively. Poor outcome was seen in 3 patients from the conservative group. CONCLUSIONS: Overall, immediate surgery yields excellent results and is superior to nonoperative treatment in the management of penile fracture. However, conservative therapy restricted to uncomplicated cases can lead to an equally good outcome.

Adult↗
PubMed2002

Persistently conserved positions in structurally similar, sequence dissimilar proteins: roles in preserving protein fold and function.

Many protein pairs that share the same fold do not have any detectable sequence similarity, providing a valuable source of information for studying sequence-structure relationship. In this study, we use a stringent data set of structurally similar, sequence-dissimilar protein pairs to characterize residues that may play a role in the determination of protein structure and/or function. For each protein in the database, we identify amino-acid positions that show residue conservation within both close and distant family members. These positions are termed "persistently conserved". We then proceed to determine the "mutually" persistently conserved (MPC) positions: those structurally aligned positions in a protein pair that are persistently conserved in both pair mates. Because of their intra- and interfamily conservation, these positions are good candidates for determining protein fold and function. We find that 45% of the persistently conserved positions are mutually conserved. A significant fraction of them are located in critical positions for secondary structure determination, they are mostly buried, and many of them form spatial clusters within their protein structures. A substitution matrix based on the subset of MPC positions shows two distinct characteristics: (i) it is different from other available matrices, even those that are derived from structural alignments; (ii) its relative entropy is high, emphasizing the special residue restrictions imposed on these positions. Such a substitution matrix should be valuable for protein design experiments.

Amino Acid Motifs↗
PubMed1999

From fold predictions to function predictions: automation of functional site conservation analysis for functional genome predictions.

A database of functional sites for proteins with known structures, SITE, is constructed and used in conjunction with a simple pattern matching program SiteMatch to evaluate possible function conservation in a recently constructed database of fold predictions for Escherichia coli proteins (Rychlewski L et al., 1999, Protein Sci 8:614-624). In this and other prediction databases, fold predictions are based on algorithms that can recognize weak sequence similarities and putatively assign new proteins into already characterized protein families. It is not clear whether such sequence similarities arise from distant homologies or general similarity of physicochemical features along the sequence. Leaving aside the important question of nature of relations within fold superfamilies, it is possible to assess possible function conservation by looking at the pattern of conservation of crucial functional residues. SITE consists of a multilevel function description based on structure annotations and structure analyses. In particular, active site residues, ligand binding residues, and patterns of hydrophobic residues on the protein surface are used to describe different functional features. SiteMatch, a simple pattern matching program, is designed to check the conservation of residues involved in protein activity in alignments generated by any alignment method. Here, this procedure is used to study conservation of functional features in alignments between protein sequences from the E. coli genome and their optimal structural templates. The optimal templates were identified and alignments taken from the database of genomic structural predictions was described in a previous publication (Rychlewski L et al., 1999, Protein Sci 8:614-624). An automated assessment of function conservation is used to analyze the relation between fold and function similarity for a large number of fold predictions. For instance, it is shown that identifying low significance predictions with a high level of functional residue conservations can be used to extend the prediction sensitivity for fold prediction methods. Over 100 new fold/function predictions in this class were obtained in the E. coli genome. At the same time, about 30% of our previous fold predictions are not confirmed as function predictions, further highlighting the problem of function divergence in fold superfamilies.

Algorithms↗
PubMed2000

The identification of conserved interactions within the SH3 domain by alignment of sequences and structures.

The SH3 domain, comprised of approximately 60 residues, is found within a wide variety of proteins, and is a mediator of protein-protein interactions. Due to the large number of SH3 domain sequences and structures in the databases, this domain provides one of the best available systems for the examination of sequence and structural conservation within a protein family. In this study, a large and diverse alignment of SH3 domain sequences was constructed, and the pattern of conservation within this alignment was compared to conserved structural features, as deduced from analysis of eighteen different SH3 domain structures. Seventeen SH3 domain structures solved in the presence of bound peptide were also examined to identify positions that are consistently most important in mediating the peptide-binding function of this domain. Although residues at the two most conserved positions in the alignment are directly involved in peptide binding, residues at most other conserved positions play structural roles, such as stabilizing turns or comprising the hydrophobic core. Surprisingly, several highly conserved side-chain to main-chain hydrogen bonds were observed in the functionally crucial RT-Src loop between residues with little direct involvement in peptide binding. These hydrogen bonds may be important for maintaining this region in the precise conformation necessary for specific peptide recognition. In addition, a previously unrecognized yet highly conserved beta-bulge was identified in the second beta-strand of the domain, which appears to provide a necessary kink in this strand, allowing it to hydrogen bond to both sheets comprising the fold.

Amino Acid Sequence↗
PubMed1997

Identification of conserved aromatic residues essential for agonist binding and second messenger production at 5-hydroxytryptamine2A receptors.

Several models of agonist binding to G protein-coupled 5-hydroxytryptamine [5-HT] (serotonin) receptors have highlighted the potential importance of highly conserved aromatic residues for ligand binding and agonist efficacy. In this study, we tested these models by constructing and characterizing a number of point mutations of conserved and nonconserved aromatic residues using the 5-HT2A receptor as a model system. Mutations of three highly conserved tryptophans (W200A, W336A, and W367A) proposed to reside near the binding pocket markedly reduced agonist affinity and efficacy at 5-HT2A receptors. Mutations of two other highly conserved aromatic residues postulated to be near the agonist binding site (F340L and Y370A) also had dramatic effects on agonist binding and efficacy. Point mutations of neighboring conserved phenylalanines (F339L and F365L) had minimal effects on agonist binding, although the F365L mutation diminished agonist efficacy. Finally, mutations of two nonconserved aromatic residues (F125L and F383A) not predicted to be near the binding pocket had no effects on agonist binding, potency, or efficacy. Our results are best explained by models that suggest that helices III, V, VI, and VII can form a unit of interacting helices in which highly conserved aromatic residues are oriented toward the center of the helical aggregate to form an aromatic pocket. In addition, our novel results identify a series of aromatic residues essential for agonist-induced second messenger production. These results demonstrate that highly conserved aromatic residues residing in neighboring helices provide the optimum environment for both agonist binding and activation of 5-HT2A receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1979

Conserved region of mammalian retrovirus RNA.

The viral RNAs of various mammalian retroviruses contain highly conserved sequences close to their 3' ends. This was demonstrated by interviral molecular hybridization between fractionated viral complementary DNA (cDNA) and RNA. cDNA near the 3' end (cDNA(3')) from a rat virus (RPL strain) was fractionated by size and mixed with mouse virus RNA (Rauscher leukemia virus). No hybridization occurred with total cDNA (cDNA(total)), in agreement with previous results, but a cross-reacting sequence was found with the fractionated cDNA(3'). The sequences between 50 to 400 nucleotides from the 3' terminus of heteropolymeric RNA were most hybridizable. The rat viral cDNA(3') hybridized with mouse virus RNA more extensively than with RNA of remotely related retroviruses. The related viral sequence of the rodent viruses (mouse and rat) showed as much divergence in heteroduplex thermal denaturation profiles as did the unique sequence DNA of these two rodents. This suggests that over a period of time, rodent viruses have preserved a sequence with changes correlated to phylogenetic distance of hosts. The cross-reacting sequence of replication-competent retroviruses was conserved even in the genome of the replication-defective sarcoma virus and was also located in these genomes near the 3' end of 30S RNA. A fraction of RD114 cDNA(3'), corresponding to the conserved region, cross-hybridized extensively with RNA of a baboon endogenous virus (M7). Fractions of similar size prepared from cDNA(3') of MPMV, a primate type D virus, hybridized with M7 RNA to a lesser extent. Hybridization was not observed between Mason-Pfizer monkey virus and M7 if total cDNA's were incubated with viral RNAs. The degree of cross-reaction of the shared sequence appeared to be influenced by viral ancestral relatedness and host cell phylogenetic relationships. Thus, the strikingly high extent of cross-reaction at the conserved region between rodent viruses and simian sarcoma virus and between baboon virus and RD114 virus may reflect ancestral relatedness of the viruses. Slight cross-reaction at the site between type B and C viruses of rodents (mouse mammary tumor virus and RPL virus, 58-2T) or type C and D viruses of primates (M7, RD114, and Mason-Pfizer monkey virus) may have arisen at the conserved region through a mechanism that depends more on the phylogenetic relatedness of the host cells than on the viral type or origin. Determining the sequence of the conserved region may help elucidate this mechanism. The conserved sequences in retroviruses described here may be an important functional unit for the life cycle of many retroviruses.

Animals↗