Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “sequence diversity”

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 1,027 records · Page 57Linked to original sources
PubMed2004

Crystal structure of the Toll/interleukin-1 receptor domain of human IL-1RAPL.

The Toll/interleukin-1 receptor (TIR) domain is conserved in the intracellular regions of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs) as well as in several cytoplasmic adapter molecules. This domain has crucial roles in signal transduction by these receptors for host immune response. Here we report the crystal structure at 2.3-A resolution of the TIR domain of human IL-1RAPL, the first structure of a TIR domain of the IL-1R superfamily. There are large structural differences between this TIR domain and that of TLR1 and TLR2. Helix alphaD in IL-1RAPL is almost perpendicular to its equivalent in TLR1 or TLR2. The BB loop contains a hydrogen bond unique to IL-1RAPL between Thr residues at the 8th and 10th positions. The structural and sequence diversity among these domains may be important for specificity in the signal transduction by these receptors. A dimer of the TIR domain of IL-1RAPL is observed in the crystal, although this domain is monomeric in solution. Residues in the dimer interface are mostly unique to IL-1RAPL, which is consistent with the distinct functional roles of this receptor. Our functional studies show IL-1RAPL can activate JNK but not the ERK or the p38 MAP kinases, whereas its close homolog, TIGIRR, cannot activate JNK. Deletion mutagenesis studies show that the activation of JNK by IL-1RAPL does not depend on the integrity of its TIR domain, suggesting a distinct mechanism of signaling through this receptor.

Amino Acid Sequence↗
PubMed1995

Species-specific 18S rRNA gene amplification for the detection of P. falciparum and P. vivax malaria parasites.

Based on the sequence diversity of the Plasmodium 18S ribosomal RNA (rRNA), we designed oligonucleotide primers for polymerase chain reaction (PCR) to yield different size fragments for P. falciparum and P. vivax. The primers for the PCR procedure were chosen such that the 5' primer was Plasmodium-conserved while the 3' primers were species-specific. Using primer cocktails and cloned plasmid DNAs containing the 18S rRNA genes or parasite genomic DNA as targets, we show that the PCR procedure yields 1.4-kb and 0.5-kb DNA fragments for P. falciparum and P. vivax, respectively. Limited field testing of this procedure demonstrated the utility of a ribosomal gene based species-specific malaria diagnosis.

Animals↗
PubMed1997

Antigenicity of recombinant proteins derived from Plasmodium falciparum merozoite surface protein 1.

We have expressed seven recombinant antigens representing two N-terminal regions of the polymorphic merozoite surface protein 1 (MSP-1) of Plasmodium falciparum. The antigens include the MAD20 and Palo Alto forms of the relatively conserved Block 1 region, and variants of the Block 2 region from isolates 3D7, Palo Alto FUP, MAD20, Wellcome and RO33, that are representative of a range or amino acid sequence diversity in this most polymorphic section of MSP-1. All recombinant antigens have been able to immunise mice to produce polyclonal antibodies which specifically recognise parasite MSP-1 in indirect immunofluorescence assays and in Western blots. The recombinant antigens also react appropriately in ELISA with murine monoclonal antibodies specific for variant epitopes in Block 2 of MSP-1. These results show that the antigenic structure of the recombinant proteins is similar to that of the native MSP-1 product from parasites. Importantly, human sera from malaria-exposed individuals contain IgG antibodies that recognise very specifically one or another of the Block 2 types, showing that different Block 2 types are immunogenic, antigenically distinct and distinguishable when presented during natural infections. In contrast, the conserved Block 1 is rarely recognised by human antibodies.

Alleles↗
PubMed2004

Sequence and structure of epoxide hydrolases: a systematic analysis.

Epoxide hydrolases (EC 3.3.2.3) are ubiquitous enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. More than 100 epoxide hydrolases (EH) have been identified or predicted, and 3 structures are available. Although they catalyze the same chemical reaction, sequence similarity is low. To identify conserved regions, all EHs were aligned. Phylogenetic analysis identified 12 homologous families, which were grouped into 2 major superfamilies: the microsomal EH superfamily, which includes the homologous families of Mammalian, Insect, Fungal, and Bacterial EHs, and the cytosolic EH superfamily, which includes Mammalian, Plant, and Bacterial EHs. Bacterial EHs show a high sequence diversity. Based on structure comparison of three known structures from Agrobacterium radiobacter AD1 (cytosolic EH), Aspergillus niger (microsomal EH), Mus musculus (cytosolic EH), and multisequence alignment and phylogenetic analysis of 95 EHs, the modular architecture of this enzyme family was analyzed. Although core and cap domain are highly conserved, the structural differences between the EHs are restricted to only two loops: the NC-loop connecting the core and the cap and the cap-loop, which is inserted into the cap domain. EHs were assigned to either of three clusters based on loop length. By using this classification, core and cap region of all EHs, NC-loops and cap-loops of 78% and 89% of all EHs, respectively, could be modeled. Representative models are available from the Lipase Engineering Database, http://www.led.uni-stuttgart.de.

Amino Acid Sequence↗
PubMed2006

Application of Multi Locus Sequence Typing to the analysis of the biodiversity of indigenous Saccharomyces cerevisiae wine yeasts from Lebanon.

AIMS: To assess suitability of Multi Locus Sequence Typing (MLST) for investigating the biodiversity of wine yeast strains. This method was compared with established ones like microsatellite analysis or amplification of genomic regions flanked by repeated (delta) elements. METHODS AND RESULTS: DNA fragments were amplified and sequenced for 26 loci representing housekeeping genes, open reading frames (ORFs) of unknown functions or intergenic regions. A set of seven loci was tested on 84 Saccharomyces cerevisiae strains, including 65 strains isolated from traditional wineries in Lebanon, commercial wine strains and Asian isolates. An overall sequence diversity of 2.05% was observed, consisting of single nucleotide polymorphisms, 60% of them occurring in a heterozygous state. The number of polymorphic sites per locus varied between 4 and 14. The same set of strains was analysed by microsatellite typing on six polymorphic loci and by interdelta amplification. CONCLUSIONS: Clustering of MLST profiles clearly differentiated the Asian group of strains from Lebanese and European commercial strains that appear closely related. The current MLST scheme appears less discriminatory (92.27%) on closely related wine yeasts than microsatellite or interdelta typing (>99%). SIGNIFICANCE AND IMPACT OF THE STUDY: MLST is a highly reliable method for relatedness inference and promising for wine yeast typing.

Biodiversity↗
PubMed2004

Genes encoding candidate pheromone receptors in a moth (Heliothis virescens).

The remarkable responsiveness of male moths to female released pheromones is based on the extremely sensitive and selective reaction of highly specialized sensory cells in the male antennae. These cells are supposed to be equipped with male-specific receptors for pheromonal compounds, however, the nature of these receptors is still elusive. By using a combination of genomic sequence analysis and cDNA-library screening, we have cloned various cDNAs of the tobacco budworm Heliothis virescens encoding candidate olfactory receptors. A comparison of all identified receptor types not only highlighted their overall high degree of sequence diversity but also led to the identification of a small group of receptors sharing >40% identity. In RT-PCR analysis it was found that distinct members of this group were expressed exclusively in the antennae of male moths. In situ hybridization experiments revealed that the male-specific expression of these receptor types was confined to antennal cells located beneath sensillar hair structures (sensilla triochoidea), which have been shown to contain pheromone-sensitive neurons. Moreover, two-color double in situ-hybridization approaches uncovered that cells expressing one of these receptor types were surrounded by cells expressing pheromone-binding proteins, as expected for a pheromone-sensitive sensillum. These findings suggest that receptors like Heliothis receptor 14-16 (HR14-HR16) may render antennal cells responsive to pheromones.

Animals↗
PubMed1995

Dispersion and insertion polymorphism in two small subfamilies of recently amplified human Alu repeats.

Newly isolated members of two recently propagated (young) Alu subfamilies were examined for sequence diversity and insertion polymorphism in primate genomes. The smaller subfamily (termed HS-2) is comprised of approximately 5 to 25 members, while the larger (termed Sb2) includes approximately 125 to 600 members. Individual members of these Alu subfamilies share distinguishing sets of diagnostic mutations, are well-conserved relative to each other, and have expanded in the human lineage. At least one member from each subfamily is known to be polymorphic in humans. Three newly characterized HS-2 Alu family members as well as three Sb2 Alu repeats are monomorphic (fixed) in humans. The existence of a number of Alu subfamilies that have amplified in parallel within the human genome provides compelling evidence for the simultaneous activity of multiple dispersed Alu source genes.

Alleles↗
PubMed1997

Multiple origins of a mitochondrial mutation conferring deafness.

A point mutation (1555G) in the smaller ribosomal subunit of the mitochondrial DNA (mtDNA) has been associated with maternally inherited traits of hypersensitivity to streptomycin and sensorineural deafness in a number of families from China, Japan, Israel, and Africa. To determine whether this distribution was the result of a single or multiple mutational events, we carried out genetic distance analysis and phylogenetic analysis of 10 independent mtDNA D-loop sequences from Africa and Asia. The mtDNA sequence diversity was high (2.21%). Phylogenetic analysis assigned 1555G-bearing haplotypes at very divergent points in the human mtDNA evolutionary tree, and the 1555G mutations occur in many cases on race-specific mtDNA haplotypes, both facts are inconsistent with a recent introgression of the mutation into these races. The simplest interpretation of the available data is that there have been multiple origins of the 1555G mutation. The genetic distance among mtDNAs bearing the pathogenic 1555G mutation is much larger than among mtDNAs bearing either evolutionarily neutral or weakly deleterious nucleotide substitutions (such as the 4336G mutation). These results are consistent with the view that pathogenic mtDNA haplotypes such as 1555G arise on disparate mtDNA lineages which because of negative natural selection leave relatively few related descendants. The co-existence of the same mutation with deafness in individuals with very different nuclear and mitochondrial genetic backgrounds confirms the pathogenicity of the 1555G mutation.

Asia↗
PubMed1996

Human T-cell lymphotropic virus types I and II infections in patients with leukaemia/lymphoma and in subjects with sexually transmitted diseases in Nigeria.

Serological assays that distinguish antibodies to human T-cell lymphotropic virus types I (HTLV-I) and type II (HTLV-II), and polymerase chain reaction (PCR) tests were used to investigate association of these two human retroviruses with several well-defined clinical conditions in Nigeria. We compared the frequency of HTLV-I and HTLV-II infections among patients with lymphopholiferative disorders (n=65), individuals with various sexually transmitted diseases (n=40), patients with genitals candidiasis (n=25) and apparently healthy individuals (n=60). Serological analysis of blood samples from all four groups showed that 10 of the 190 (5.3%) individuals tested were confirmed positive for the presence of antibodies to HTLV-I(6) or HTLV-II(4). Using the PCR technique, specific HTLV-I or HTLV-II sequences were amplified from the genomic DNA of 4 of 6 HTLV-I seropositive and 3 of the 4 HTLV-II seropositive individuals respectively. However, sequences of both viruses were amplified from the genomic DNAs of the remaining 3 seropositive individuals. Since one of the 5 sets of primer pairs [SK110(II)/SK111(II)], which is used for specific identification of HTLV-II did not amplify the target sequence from the genomic DNAs of any of the 4 HTLV-II confirmed seropositive individuals in this study, it suggested sequence diversity of these viruses in Nigeria. The virus-infected individuals identified in this study were one (1.5%) of the 65 patients with leukaemia/lymphoma (HTLV-I), 6 of 40 (15.0%) individuals (HTLV-I = 1 , HTLV-II = 3, HTLV-I/II = 2) with sexually transmitted diseases (STD), one of 25(4.0%) subjects with genital candidiasis for HTLV-I and 2 of 60 (33.3%) healthy individuals (one for HTLV-I and one for HTLV-I/II). There was a significant difference (P < 0.025) between the prevalence of HTLV-I/II infections among patients with lymphoma/leukaemia and those who attended STD clinic in Ibadan, Nigeria. This study also suggests that while HTLV-I and HTLV-II may be important sexually transmitted viruses, they may not be specific aetiological agents of the common lymphoproliferative disorders in Nigeria.

Adult↗
PubMed2004

A comparison of sequence-based polymorphism and haplotype content in transcribed and anonymous regions of the barley genome.

Direct estimates of sequence diversity provides an abundant source of DNA polymorphisms based on single nucleotide polymorphisms (SNPs). The frequency and distribution of nucleotide diversity within 23 genes associated with grain germination in barley were determined in a sample of accessions representing European cultivars, landraces, and wild barley accessions from throughout the fertile crescent. The overall nucleotide diversity ranged from 0.0021 to 0.0189 with a single nucleotide change being detected every 78 bp and insertion-deletion events being observed every 680 bp. Within the cultivated (H. vulgare) genepool, a small number of haplotypes were detected, the total number of haplotypes observed in H. spontaneum was almost double that detected in H. vulgare (46 and 26, respectively). Distinct haplotypes were observed in the H. spontaneum and landrace genepools, which are highly divergent from H. vulgare. A comparison of SNP-based haplotype data with EST-derived SSRs and genomic SSRs revealed a similar trend of decreasing variability in the cultivated genepool. However, the number of unique alleles identified in the cultivated sample was much greater with genomic SSRs (18%) compared with only 2.1% for SNPs and 3.8% for EST-derived SSRs. The potential utility of SNPs and EST-derived SSRs for association mapping in barley is discussed.

Base Sequence↗
PubMed1996

Characterization of Serpulina hyodysenteriae isolates of serotypes 8 and 9 by random amplification of polymorphic DNA analysis.

A PCR-based DNA fingerprinting method termed RAPD (Random Amplification of Polymorphic DNA), or AP-PCR (for Arbitrary Primed PCR) was used to detect sequence diversity among reference strains and isolates of Serpulina hyodysenteriae. RAPD fingerprinting of 20 S. hyodysenteriae isolates of serotypes 8 or 9 from Quebec was generated with 2 different 10-base primers used independently. Reference strains and field isolates belonging to serotypes 8 or 9 revealed polymorphisms in RAPD fingerprints with both primers. Interspecies polymorphisms were observed by RAPD analysis of S. hyodysenteriae representing serotypes 1 to 9, S.innocens, and 5 other weakly beta-hemolytic intestinal spirochetes. A dendrogram based on the analysis of RAPD profiles of the strains tested with one of the primers (#17), permitted the clustering of these strains into 11 divisions. The predominance of particular RAPD profiles among S. hyodysenteriae isolates isolated from cases of swine dysentery in different herds suggested that certain S. hyodysenteriae types could be epidemiologically important. Our results indicate that RAPD could be used as a typing method for S. hyodysenteriae and as an epidemiological method for identifying spirochetes isolated from swine.

Base Sequence↗
PubMed1997

Structural requirement of highly-conserved residues in globins.

Globins have remarkable sequence diversity, and yet maintain a common fold. In spite of the diversity, there are highly-conserved residues at several sites. The conserved residues were examined in terms of the structural stability, by employing the pseudo-energy functions of the structure/sequence compatibility method. The fitness of each residue type to the structural environment was evaluated at seven highly-conserved sites: the Leu (at the B10 site), Phe (CD1), and Leu (F4) residues were found to fit their respective sites due to hydrophobic interactions; Pro (C2) stabilizes the N-terminal edge of an alpha-helical structure; and Phe (CD4) is stabilized by backbone hydrogen-bonding to Phe (CD1). On the other hand, the other two residues, His (E7) and His (F8), are poorly suited to the sites from a structural viewpoint, suggesting that their conservation clearly results from a heme-related functional requirement. The invariant Phe residue (CD1) has been suggested to be important for supporting the heme. The present analysis revealed that this residue is also well suited to the site in terms of energy.

Amino Acid Sequence↗
PubMed2001

Characterisation of the long terminal repeat regions of South African human immunodeficiency virus type 1 isolates.

The 5' long terminal repeat (LTR) region of the integrated proviral human immunodeficiency virus type I (HIV-1) template encodes cis-acting sequences for cellular proteins that are responsible for initiating viral transcription. The objective of this study was to analyse the LTR regions of isolates from a broad spectrum of South African HIV-1 infected individuals to (i) determine if sequence diversity was sufficient to allow for subtyping on the basis of this region, and (ii) to note any specific or unusual alterations in promoter binding motifs that may be common to this group of isolates or specific HIV-1 subtypes within this group. A total of 60 isolates were subtyped by heteroduplex mobility assay (HMA) and by phylogenetic analysis, using both the env and gag regions. Phylogenetic relatedness within the LTR region demonstrated the suitability of this region for use in HIV-1 subtype designation. The presence of additional NF-kappaB binding elements as well as altered USF binding sites were features common to subtype C HIV-1 isolates. Although the biological relevance of these alterations within the HIV-1 LTR with respect to viral replicative capacity and patient disease progression is unknown, there is strong support to suggest that in the presence of these features, there is increased gene transcription in subtype C isolates, and that this would be further increased in the presence of secondary infection.

Base Sequence↗
PubMed1992

Detection and differentiation of bovine group A rotavirus serotypes using polymerase chain reaction-generated probes to the VP7 gene.

Dot and Northern blot hybridization assays were developed to detect and differentiate group A bovine rotavirus serotypes using radiolabeled serotype 6 (Nebraska calf diarrhea virus [NCDV] and United Kingdom [UK] strains) or serotype 10 (Crocker [Cr] strain) VP7 gene probes. Partial length VP7-specific cDNA encompassing areas of major sequence diversity were generated by the polymerase chain reaction (PCR) using either cloned VP7 genes (NCDV and UK strains) or reverse transcribed mRNA (Cr strain) as templates. Radiolabeled probes prepared from the PCR-generated cDNA were tested at various stringency conditions to optimize the hybridization assays. At high stringency conditions (52 C, 50% formamide, 5 x standard saline citrate), the NCDV, UK, and Cr probes serotypically differentiated bovine rotavirus isolates in RNA samples prepared from cell culture propagated viruses or in fecal specimens from infected gnotobiotic calves. The sensitivity and specificity of NCDV and Cr VP7 probes were characterized in dot blot hybridization assays, and the probes were estimated to detect at least 1 ng of viral RNA. The serotyping results obtained using VP7 probes were similar to those obtained using serologic assays. Further development of these assays may provide a useful means for the rapid detection and differentiation of bovine rotavirus serotypes in fecal samples from calves in the field.

Animals↗
PubMed2004

Molecular phylogenetic status of the Korean goral and Japanese serow based on partial sequences of the mitochondrial cytochrome b gene.

To investigate the molecular phylogenetic status of the Korean goral, Nemorhaedus caudatus raddeanus, and Japanese serow, Capricornis crispus, we determined partial sequences of the mitochondrial cytochrome b gene of twelve Korean gorals and sixteen Japanese serows, and compared them with those of the major lineages of Rupicaprini species including two other Nemorhaedus species and two other Capricornis species. The Korean gorals examined possessed two haplotypes with only one nucleotide difference between them, while the Japanese serows showed slightly higher sequence diversity with five haplotypes. Genetic distances and molecular phylogenetic trees indicated that there is considerable genetic divergence between the Korean goral and N. caudatus (the Chinese goral) [Groves and Shields (1996)], but virtually none between Korean and Russian gorals. The Korean and Russian gorals may therefore be distinct from the Chinese goral. The data highlight the importance of conservation of the goral populations of these regions, and the need to reconsider the taxonomic status of Korean and Russian gorals. Our study also clearly demonstrated sufficient genetic distance between serows and gorals to justify their assignment to separate genera. Of the three species of Capricornis, the Formosan serow, C. swinhoei is more closely related to C. sumatraensis than to the Japanese serow, suggesting that the Formosan serow is a distinct species. Preliminary data on intraspecific genetic variation in the Japanese serow are also presented.

Animals↗
PubMed1998

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline.

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

Base Sequence↗
PubMed2003

Endogenous tryptophan residues of cAPK regulatory subunit type IIbeta reveal local variations in environments and dynamics.

The amino terminal dimerization/docking domain and the two-tandem, carboxy-terminal cAMP-binding domains (A and B) of cAMP-dependent protein kinase regulatory (R) subunits are connected by a variable linker region. In addition to providing a docking site for the catalytic subunit, the linker region is a major source of sequence diversity between the R-subunit isoforms. The RIIbeta isoform uniquely contains two endogenous tryptophan residues, one at position 58 in the linker region and the other at position 243 in cAMP-binding domain A, which can act as intrinsic reporter groups of their dynamics and microenvironment. Two single-point mutations, W58F and W243F, allowed the local environment of each Trp to be probed using steady-state and time-resolved fluorescence techniques. We report that: (a) the tryptophan fluorescence of the wild-type protein largely reflects Trp243 emission; (2) cAMP selectively quenches Trp243 and thus acts as a cAMP sensor; (3) Trp58 resides in a highly solvated, unstructured, and mobile region of the protein; and (4) Trp243 resides in a stable, folded domain and is relatively buried and rigid within the domain. The use of endogenous Trp residues presents a non-perturbing method for studying R-subunit subdomain characteristics in addition to providing the first biophysical data on the RIIbeta linker region.

Amino Acid Sequence↗
PubMed2003

Phylogeography of the coronulid barnacle, Chelonibia testudinaria, from loggerhead sea turtles, Caretta caretta.

The barnacle, Chelonibia testudinaria, is a common inhabitant of the marine turtle epibiont community and plays a key role in the development of this community. Phylogeographic analysis of 79 cytochrome c oxidase I (COX1) sequences for barnacles collected from five populations found contrasting patterns of divergence for populations in the Atlantic vs. the Pacific Ocean. Our analysis indicates that the two Pacific populations, Senri Beach, Japan and Bahia Magdalena, Mexico, were not only highly divergent from the Atlantic populations but are highly divergent from one another. We suggest that barnacles from these populations may represent cryptic species. In contrast, sequence divergence was greatly reduced among barnacles collected from Wassaw Island, GA, USA, Keewaydin, FL, USA, and Kyparissia, Pèloponnésus Island, Greece. A reduction in sequence diversity at the latter site was attributed to a recent range expansion into the Mediterranean Sea. We examined historical patterns of migration among the three Atlantic and Mediterranean populations using the program migrate. This analysis indicates a high rate of migration from Keewaydin to Wassaw Island, contrasted with a much lower rate of migration in the opposite direction. The estimated migration rate from Kyparissia to Keewaydin was also non-negligible. We suggest that the association between C. testudinaria and loggerhead turtles and the patterns of turtle migration have played key roles in the expansion of the range of C. testudinaria into the Mediterranean Sea and the subsequent patterns of barnacle migration. We further propose that the difference between ocean basins, with respect to the impact of host migration on barnacle gene flow, probably stems from the fact that host-mediated dispersal in the Atlantic depends on advanced stage juveniles and adults while any host-mediated dispersal in the Pacific would have to involve early "pelagic" stage juvenile loggerheads.

Animal Migration↗