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PubMed2004

Inter- and intragenus structural variations in caliciviruses and their functional implications.

The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity and strain diversity, we performed structural studies of the recombinant capsid of Grimsby virus, the recombinant capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4), which are representative of the genera Norovirus (genogroup 2), Sapovirus, and Vesivirus, respectively. A comparative analysis of these structures was performed with that of the recombinant capsid of Norwalk virus, a prototype member of Norovirus genogroup 1. Although these capsids share a common architectural framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral lattice with a modular domain organization of the subunit consisting of a shell (S) domain and a protrusion (P) domain, they exhibit distinct differences. The distally located P2 subdomain of P shows the most prominent differences both in shape and in size, in accordance with the observed sequence variability. Another major difference is in the relative orientation between the S and P domains, particularly between those of noroviruses and other caliciviruses. Despite being a human pathogen, the Parkville virus capsid shows more structural similarity to SMSV4, an animal calicivirus, suggesting a closer relationship between sapoviruses and animal caliciviruses. These comparative structural studies of caliciviruses provide a functional rationale for the unique modular domain organization of the capsid protein with an embedded flexibility reminiscent of an antibody structure. The highly conserved S domain functions to provide an icosahedral scaffold; the hypervariable P2 subdomain may function as a replaceable module to confer host specificity and strain diversity; and the P1 subdomain, located between S and P2, provides additional fine-tuning to position the P2 subdomain.

Amino Acid Sequence↗

PubMed1993

Structural variation of the anterior and posterior anulus fibrosus in the development of human lumbar intervertebral disc. A risk factor for intervertebral disc rupture.

A morphologic comparison of the laminated structure of the anterior and posterior anulus fibrosus of lumbar intervertebral disc was made on 24 L3-4 and L4-5 discs obtained from 10 fetus, one child, and one young adult cadavers. Low power microscopic and polarized microscopic observations and measurements on the transverse sections were performed to assess 1) lamellar bundle arrangement, 2) number of distinct lamellar bundles, 3) percentage of incomplete lamellar bundles, and 4) fiber-interlacing angles. The number of lamellar bundles was greater in the anterior anulus than in the posterior anulus. A very complex structure was observed in the posterior middle anulus in all the specimens, with a high percentage of incomplete/discontinuous lamellar bundles and greater fiber-interlacing angles. Loose connection of the lamellar bundles of posterior outer anulus was observed in fetal discs. The annular strength was not measured in the present study, however, the risk of posterior disc rupture in the young may be influenced by an inherent structural variation with a weak posterior anulus fibrosus.

Adult↗

PubMed1991

Structural variations produced in vitro by gonadotrophins and steroid hormones on the cell surfaces of the ovarian epithelium of the chick embryo.

The purpose of the present work was to analyze the structural variations produced "in vitro" by hormones on the cell surfaces of the ovarian epithelium of the chick embryo, in relation to the growth of the left ovary and atrophy of the right one. Explants of both ovaries from embryos at 7 to 19 days of development were separately cultured for 4 days in MEM with 10% of fetal bovine serum (control), and plus 17-beta-estradiol, testosterone propionate, progesterone, FSH, LH or hCG added individually to cultures (experimental). The cultures were processed for their structural, ultrastructural and cytochemical study. In control cultures, membrane differentiations and mucosubstances were similar in both ovaries and at all ages to those in ovo. 17-beta-estradiol produced a greater development of microvilli, junctional complexes and mucin in the epithelial cells and interdigitations in the germ cells of the left ovary, while in the right gonad there was cell regression. Testosterone and progesterone evoked in the left gonad a response similar to that obtained with the estrogen, whereas in the right ovary no changes were observed with respect to controls. FSH led to cellular regression in both ovaries. Finally, with LH or hCG the changes produced in the left ovary were similar to those induced by the estrogen, and in the right one an increase of membrane differentiations and of mucosubstances related to them was found in comparison to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Glucose-6-phosphate dehydrogenase. Characterization of a reactive lysine residue in the Pichia jadinii enzyme reveals a limited structural variation in a functionally significant segment.

Glucose-6-phosphate dehydrogenase from the yeast Pichia jadinii has a reactive lysine residue in a segment of amino acid sequence Ile-Asp-His-Tyr-Leu-Gly-Lys*-Glu-Met-Val-Lys. This structure differs from that of other characterized glucose-6-phosphate dehydrogenases, but outside yeasts the segment is invariant in known mammalian, insect and bacterial forms. Thus, limited structural variation is now defined within yeasts for a part of the protein otherwise strictly conserved, and for which stringent structural requirements probably relate to enzymic mechanisms.

Amino Acid Sequence↗

PubMed1987

Structural variations in the alanine-rich antifreeze proteins of the pleuronectinae.

The sequence and activity of antifreeze proteins from two right eye flounder species were compared to assess the influence of structural variations on antifreeze capacity. The cDNA encoding the major serum antifreeze protein in the yellowtail flounder (Limanda ferruginea) was cloned from liver tissue. Its DNA sequence shows that the precursor to the antifreeze is a 97-residue preproportion. Edman degradation identified the N-terminus of the 48-amino-acid mature serum antifreeze protein and confirmed the sequence of the first 36 residues. A comparison with the previously determined winter flounder antifreeze protein and mRNA sequences shows strong homology through the 5' and 3' untranslated regions and in the peptide region. The mature protein section has the greatest sequence variation. Specifically, the yellowtail antifreeze protein, in contrast to that of the winter flounder, contains a fourth 11-amino-acid repeat and lacks several of the hydrophilic residues that have been postulated to aid in the binding of the protein to ice crystals. Intramolecular salt bridges are present in the antifreeze proteins from both species but in different registries with respect to the 11-amino-acid repeats. On a mass basis the yellowtail flounder antifreeze, though longer than that of the winter flounder, is only 80% as effective at depressing the freezing temperature of aqueous solutions. This lower activity might be due to the reduced number of hydrophilic ice-binding residues per molecule.

Alanine↗

PubMed2006

Dependence of DNA electronic structure on environmental and structural variations.

We present experimental and theoretical evidence that varying the local environment and physical structure of dried DNA has a direct impact on its electronic structure. By preparing samples of DNA in various solutions, it was possible to alter the type of ions present during the production of the DNA samples. These variations resulted in differences in the local chemical environment of the dried DNA molecules. X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES) were used to probe the variations in the electronic structure of DNA samples. DFT calculations of a stack of 10 adenine (A)-thymine (T) nucleobase pairs show that slight structural variations in stacking height have a direct influence on the electronic structure and result in changes to the HOMO-LUMO gap. The effects of these differences in the local environment on the electronic structure are discussed and are related to the results of conductivity measurements of DNA.

DNA↗

PubMed1996

Conformational heterogeneity in two regions of TAT results in structural variations of this protein as a function of HIV-1 isolates.

TAT protein is an essential regulatory protein of the human immunodeficiency virus type 1 (HIV-1). Inhibition of TAT activity blocks the virus cycle, and a drug that blocks TAT is one of the possibilities to cure AIDS. Circular dichroism (CD) was measured for TAT peptides covering the TAT sequence with overlaps. The CD spectrum of each peptide was measured in different solvents to evaluate the ability of each TAT region to form different secondary structures. The most variation or conformational heterogeneity is observed with the two regions adjacent to the TAT basic region. CD data show that the basic region can adopt an extended structure in a full TAT protein, which is not the case for the isolated peptide. TAT sequences from the different HIV-1 isolates were analyzed, and the results showed that the sequences could be gathered into six groups. Molecular modeling was done on the various isolates based on a TAT structure from two-dimensional NMR. After minimization and dynamic steps, the modeled three-dimensional structures were compared. The results showed structural variations of the TAT protein as a function of the HIV-1 isolates. These structural variations were mainly in the two regions adjacent to the basic region, confirming the conformational heterogeneity indicated by the CD measurements. Furthermore, Chou-Fasman analysis shows significant changes in propensities for each secondary structure only for regions III and V. This conformational heterogeneity should be essential for TAT activity and points out that regions III and V are a poor potential target to design a TAT ligand. We propose a target involving TAT structurally conserved regions, accessible whatever the size of the TAT C terminus.

Amino Acid Sequence↗

PubMed2002

Structural variation in the Waxy gene and differentiation in foxtail millet [Setaria italica (L.) P. Beauv.]: implications for multiple origins of the waxy phenotype.

The origin and evolution of the waxy type of foxtail millet [Setaria italica (L.) P. Beauv] were studied by analyzing structural variation in the Waxy gene. Initially, the Waxy gene was amplified by RT-PCR, RACE and genomic PCR from a non-waxy strain to determine the structure of the wild-type gene. Secondly, we screened by PCR for polymorphisms at the Waxy locus in 79 strains with various waxy phenotypes. We then carried out genomic Southern analysis on 67 strains and identified seven RFLP classes which were designated as types I-VII. RFLP type was correlated with phenotype, such that types I and II corresponded to non-waxy, types III and VI to low-amylose, and types IV, V and VII to waxy phenotypes. The differences between RFLP types could be attributed to insertions in the Waxy gene. Types II and VI were caused by the insertion of a Tourist element into intron 1 and a SINE-like sequence into intron 12, respectively. Types III, IV, V and VII were characterized by the insertion of large sequences into the Waxy gene that may alter the expression of the gene. Thus, multiple, independent insertions in the Waxy gene appear to have caused the loss-of-function waxy phenotypes. Furthermore, the geographical distributions of the three RFLP types associated with the waxy phenotype (types IV, V and VII) were distinct, with type IV being found mainly in Taiwan and Japan, type V in Korea, and type VII in Myanmar. These results indicate a polyphyletic origin for the waxy phenotype in landraces of foxtail millet.

Base Sequence↗

PubMed1983

Evidence for minor structural variations of class II genes in wild and inbred mice.

We organized 29 B10.W lines into eight antigenic groups on the basis of similarities in the antigenic phenotypes of their class II antigens. Tryptic peptide fingerprint comparisons of class II antigens in different antigenic groups detected structural variations in 30 to 60% of the tryptic peptides. In contrast, less than 10% of the tryptic peptides were distinguishable in comparisons of class II antigens within the same antigenic group. These results suggest structurally discrete allelic families of class II genes exist in wild mouse populations.

Animals↗

PubMed1986

Demonstration of structural variation in rat incisor dentin as determined by the x-ray Laue method.

Rat incisor dentin was studied by an x-ray micro-Laue method to investigate the relationship between crystal orientation and structural variation in the dentin. The results showed that crystal orientation was very poor in the labial dentin, but that the crystals were well-oriented in the lingual dentin. In the lingual dentin, the axis of crystal orientation was parallel to the tooth axis. It is suggested that the difference in crystal orientation between the lingual and labial dentin is due to the different mode of calcification between the two.

Animals↗

PubMed2004

Structural variations of piritrexim, a lipophilic inhibitor of human dihydrofolate reductase: synthesis, antitumor activity and molecular modeling investigations.

Piritrexim (PTX) (1), a lipophilic inhibitor of the human dihydrofolate reductase, has been evaluated as an anticancer agent. The synthesis of four structural variations (2-5) of PTX is reported. The PTX analogues 2-5 were obtained by reaction of suitable C3-building blocks with pyrimidine-2,4,6-triamine (14) or with cyanacetamide (7) and guanidine (10). The evaluation of 2-4 for antitumor activity against a panel of 60 human cancer cell lines showed inhibitory effects on the growth of the cell lines. These data are supported by molecular modeling and docking studies, which show that compounds 2-4 share the same binding mode within the DHFR active site. Moreover, the estimated ligand binding energies are in good agreement with the experimental activity data.

Antineoplastic Agents↗

PubMed1983

Sequence-dependent structural variations in two right-handed alternating pyrimidine-purine DNA oligomers in solution determined by nuclear Overhauser enhancement measurements.

A 500 MHz 1H-n.m.r. study on two right-handed self-complementary double-stranded alternating pyrimidine-purine oligodeoxyribonucleotides, 5'dCGTACG and 5'dACGCGCGT, is presented. Using the proton-proton nuclear Overhauser effect, proton resonances are assigned by a sequential method and a large number of interproton distances, both intra- and internucleotide, are determined (113 for 5'dCGTACG and 79 for 5'dACGCGCGT). The general procedure required to solve the three-dimensional solution structures of oligonucleotides from such distance data is outlined and applied to these two oligonucleotides. In the case of both oligonucleotides the overall solution structure is that of B DNA, namely a right-handed helix with a helical rise of approximately 3.3 A, 10 bp per turn and the base pairs approximately perpendicular to the helix axis. In the case of 5'dCGTACG, subtle local structural variations associated with the pyrimidine and purine nucleotides are superimposed on the overall structure but the mononucleotide repeating unit is preserved. In contrast, 5'dACGCGCGT has a clear alternating structure with a dinucleotide repeat, alternation occurring in the local helical twist and the glycosidic bond, sugar pucker and phosphodiester backbone conformations.

DNA↗

PubMed2002

Influence of structural variations in 1-alkyl(aralkyl)-3-methylimidazolium hexafluorophosphates and bis(trifluoromethyl-sulfonyl)imides on physical properties of the ionic liquids.

A series of twenty four 1-alkyl(aralkyl)-3-methylimidazolium hexafluorophosphates and bis(trifluoromethyl-sulfonyl)imides are prepared and the influence of structural variations in the imidazolium cation and the identity of the anion on physical properties (phase transition, density, viscosity, and surface tension) of the ionic liquids is determined.

Journal Article↗

PubMed1991

Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse.

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP-MF) at the midseptotemporal level correlates negatively with two-way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP-MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP-MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2). In 19 random-bred mice (9 male, 10 female), the extent of the IIP-MF showed negative correlations with swimming time after platform reversal (day 4: r = -0.50, P < .03; day 5 r = -0.73, P < .001), but none during acquisition of the task. In addition, statistical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1-3, and a significantly faster swimming time in the strain C57BL/6 (with large IIP-MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP-MF in both strains. Finally, variations of the IIP-MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP-MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.

Animals↗

PubMed1966

Immunoglobulin structure: variation in the sequence of Bence Jones proteins.

Analysis of the amino acid sequence of one Bence Jones protein is almost comtplete. Many points of interchange occur in the amino terminal. portion of the molecule relative to partial-sequence data for other proteins. Most, but not all, are, compartible with one-step mutations. Such structural variation in immunoglobulin light chains may result from many related genes.

Amino Acid Sequence↗

PubMed2026

Complex structural variation, phylogeny, and disease associations of the mucin pangenome.

Mucins are large glycoproteins that provide hydration and barrier function to epithelial tissues. Although genetically heterogeneous, all mucins harbor a large exon composed of variable number tandem repeats (VNTRs). Short-read sequencing has limited our understanding of mucin VNTR diversity and makes disease association studies challenging. We leverage 296 long-read phased genome assemblies to characterize 14 mucin family members, achieving ≥97% accuracy across 572 haplotypes. Phylogenetic haplogroup analysis reveals extraordinary structural heterozygosity, with MUC4 harboring the greatest allelic diversity (n=240 distinct lengths) and MUC12 the greatest size range (Δ = 55,233 bp; 23,080 amino acids). Ten mucins show significant population stratification (pFDR < 0.05). At the MUC4/MUC20 locus, we characterize higher-order structural variation, including a recurrent inversion, copy number variation, and interlocus gene conversion. Optimized genotyping achieves ≥95% haplogroup concordance across 10 loci. We apply this to 4,637 deeply phenotyped cystic fibrosis patients and identify a significant association between short MUC1 VNTRs and severe disease (p=0.0056), demonstrating the pangenome's utility for complex locus genotyping and disease discovery.

Journal Article↗

PubMed2026

Pan-genome-based resequencing of 2,320 accessions reveals structural variations and accelerates breeding advances in cultivated peanut.

The cultivated peanut is a crucial global legume crop that is essential for food security and nutrition, particularly in developing regions. However, its limited genetic variation hampers breeding progress and yield improvement. Here we constructed a graph-based pan-genome for peanut, incorporating 14 genomes that represent all 6 peanut varieties. Using this pan-genome, we genotyped 2,320 accessions, covering 88.03% of ICRISAT and 59.21% of USDA core germplasm, enriching valuable resources for genomic studies and breeding. We cataloged genomic structural variations and investigated the role of homoeologous exchanges in population divergence. Through our pan-genome approach, we overcame the challenges of genotyping posed by homoeologous exchanges and identified key genes associated with flowering and dwarfism in peanut. By integrating superior haplotypes and germplasm resources guided by the pan-genome, we further developed high-yield dwarf lines. This work provides essential genomic resources to accelerate functional gene discovery and modern peanut breeding.

Journal Article↗

PubMed2025

Substantial non-homologous recombination and structural variation results from Brassica AABC and CCAB hybrid meiosis.

Meiotic crossovers contribute to genetic diversity and play a crucial role in homologous chromosome segregation. Non-homologous crossovers in Brassica, involving the exchange of genetic material between genomes, can be valuable for transferring novel traits or characteristics between Brassica species. However, there are a limited number of studies that specifically investigate crossover frequencies in populations of interspecific hybrids. We investigated the distribution and frequency of homologous crossover events, as well as non-homologous recombination and structural variation, in hybrids between B. juncea (AABB) × B. napus (AACC) (resulting in AABC hybrids; 5 genotypes) and B. napus (AACC) × B. carinata (BBCC) (resulting in CCAB hybrids; 4 genotypes). The analysis was performed on individuals derived from microspore culture of both unreduced and reduced gametes produced by the AABC and CCAB hybrids. All AABC and almost all CCAB unreduced gamete-derived individuals and most AABC and CCAB reduced gamete-derived individuals showed copy number variation indicative of non-homologous (A-C) recombination. Additionally, a higher frequency of homologous crossovers, also in centromeric and pericentromic regions, was observed in the diploid genomes of the AABC and CCAB hybrids. Overall, these hybrid types show high frequencies of A-C introgressions, which may be useful in B. juncea or B. carinata introgression breeding, and this increased recombination frequency may help break up existing linkage disequilibrium blocks in the Brassica A and C genomes.

Meiosis↗