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At least 163 records · Page 9Linked to original sources

FLOWERING LOCUS C mediates natural variation in the high-temperature response of the Arabidopsis circadian clock.

Temperature compensation contributes to the accuracy of biological timing by preventing circadian rhythms from running more quickly at high than at low temperatures. We previously identified quantitative trait loci (QTL) with temperature-specific effects on the circadian rhythm of leaf movement, including a QTL linked to the transcription factor FLOWERING LOCUS C (FLC). We have now analyzed FLC alleles in near-isogenic lines and induced mutants to eliminate other candidate genes. We showed that FLC lengthened the circadian period specifically at 27 degrees C, contributing to temperature compensation of the circadian clock. Known upstream regulators of FLC expression in flowering time pathways similarly controlled its circadian effect. We sought to identify downstream targets of FLC regulation in the molecular mechanism of the circadian clock using genome-wide analysis to identify FLC-responsive genes and 3503 transcripts controlled by the circadian clock. A Bayesian clustering method based on Fourier coefficients allowed us to discriminate putative regulatory genes. Among rhythmic FLC-responsive genes, transcripts of the transcription factor LUX ARRHYTHMO (LUX) correlated in peak abundance with the circadian period in flc mutants. Mathematical modeling indicated that the modest change in peak LUX RNA abundance was sufficient to cause the period change due to FLC, providing a molecular target for the crosstalk between flowering time pathways and circadian regulation.

Arabidopsis↗

Natural variation in mite antigen density in house dust and relationship to residential factors.

To investigate the year-to-year variation of mite antigen density (Der p I, Der fI) in dust from mattresses and the relevance of residential factors for antigen load, information derived from an epidemiologic study including two surveys carried out in the households of a cohort of elementary school children (n = 1291) was analysed. When considering residences with measurements taken in both years in question (n = 1050), rank-correlation indicated a predominance of stability for both antigens (Der p I: rs = 0.82, P = 0.0001; Der f I: rs = 0.72, P = 0.0001). Using multiple regression analyses, significant associations between antigen concentrations and a variety of residential factors were found. Use of a blanket of animal hair, use of a cover or underblanket, wet spots in the bedroom, higher relative humidity and a low storey level were significantly associated with increased concentrations of Der p I, whereas inverse relationships between this antigen and room temperature, number of persons per m2 as well as use of underfloor heating were seen. Regarding Der fI, older mattresses, use of a cover or underblanket, higher weight of sampled dust, high educational level and higher ratio of inhabitants per m2 were significantly associated with increased concentrations of the antigen. On the other hand, lower Der fI concentrations were found when interior sprung mattresses were used and when the mattress was 'treated regularly'. In conclusion, two measurements, 1 year apart from each other, show that stability of mite antigen concentrations predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Natural variation in GmSOP5 regulates seed oil and protein content during soybean domestication.

Seed oil content, protein content, and yield are agronomically important, correlated traits that determine the economic value of soybean (Glycine max). However, improving seed quality and yield simultaneously is challenging because gains in one breeding target often compromise the other, and the genetic basis of this trade-off is poorly understood. Here, we performed a genome-wide association study of 429 diverse soybean accessions and identified Seed Oil and Protein 5 (SOP5), which encodes a kinesin protein, as a key locus associated with seed oil and protein content. Knockout and overexpression experiments demonstrated that GmSOP5 positively affects seed oil content and 100-seed weight and negatively influences seed protein content. GmSOP5 is located in a selective sweep region, and the domestication-related GmSOP5H1 allele is nearly fixed in cultivated soybean, contributing to increased seed size, weight, and oil content and reduced protein content. Field trials demonstrated that neither loss-of-function GmSOP5-edited mutants, which have increased seed protein content, nor GmSOP5-overexpression lines, which have increased seed oil content, differed significantly in yield from wild-type plants, because changes in plant architecture were offset by changes in seed weight. Our results shed light on soybean domestication and suggest how pleiotropy can be harnessed in breeding to enhance seed quality without compromising yield.

GWAS↗

Genetic interactions and natural variation underlying S-RNase-independent unilateral incompatibility in Solanum.

Pistils of self-incompatible (SI) species/populations typically reject pollen of related self-compatible (SC) species/populations, but not vice versa, a pattern known as unilateral incompatibility (UI). UI is complex and includes both S-RNase-dependent and S-RNase-independent mechanisms. Pistils of Solanum pennellii LA0716 (SC, no S-RNase) reject pollen of cultivated tomato, Solanum lycopersicum (SC); UI in this system involves the expression of ornithine decarboxylase2 (ODC2) and HT-A/-B genes in the pistil, and farnesyl pyrophosphate synthase2 (FPS2), ui6.2, and ui12.2 in pollen. We show that IL12-3 (HT-A/-B) × IL3-3 (ODC2) double introgression lines reject S. lycopersicum pollen, while odc2 or ht-a mutants do not, demonstrating that ODC2 and HT-A are required for UI. Transmission ratio distortion in favor of pennellii alleles was observed in interspecific F2 S. lycopersicum × S. pennellii near ui6.2 and ui12.2, and in F2 IL12-3 × IL3-3 near ui12.2. Equivalent populations made with odc2 mutants segregate in Mendelian ratios, while ht-a mutants have little effect, indicating ui6.2 and ui12.2 interact primarily with ODC2. Pollen from fps2 mutants in S. pennellii LA0716 are incompatible on pistils of all tested S. pennellii and some Solanum habrochaites accessions, but compatible with all other tomato clade species, suggesting ODC2-dependent UI evolved in a common ancestor to S. pennellii and S. habrochaites. Within S. habrochaites, fps2 pollen rejection was observed mainly in SI or mixed mating populations, suggesting an association with outcrossing. Triple mutants of S. pennellii and S. habrochaites lacking functional ODC2, HT-A/-B, and S-RNase are cross-compatible as female parents with S. lycopersicum, allowing transfer of their cytoplasmic genomes into cultivated tomato.

Solanum↗

Natural variation in SL6 determines fatty acid components and seed longevity in rice.

Seed longevity (SL) is vital for ensuring food security worldwide. However, the genetic basis of SL has been scarcely documented. Here, we report the cloning of a major SL locus, qSL6, encoding a fatty acyl-ACP thioesterase type B. SL6 is functionally conserved in regulating palmitic acid synthesis in seeds, conferring higher oxidation durability and SL in various species. Through the VP1-SL6 module, a seed desiccation-derived ABA signal is transmitted via VP1, which directly activates SL6 transcription to alter the fatty acid composition and elevate SL in seeds. The ancestral elite allele SL6HHZ harbors a virus-derived CT-rich motif cis-element in the 5'UTR, which serves as a universal, bidirectional mRNA stabilizer, contributing to the divergence between indica and japonica in terms of SL. Moreover, manipulating SL6 expression via marker-assisted selection or transgenic approaches notably improved SL in rice cultivars and F1 hybrids without affecting major agronomic traits. Our findings provided a promising genetic locus for improving SL in rice.

Oryza↗

Natural variation of canine parvovirus.

Canine parvovirus was first recognized during 1978. Analysis of isolates collected since its emergence revealed that viruses circulating after 1980 were antigenically different from earlier isolates. Monoclonal antibodies clearly distinguished the two strains, some being specific for either the old or the new viruses. Restriction enzyme analysis of viral DNA's showed that the post-1980 viruses were similar to earlier isolates, but some restriction site differences were present in the new strain. These results suggest that the canine parvoviruses infecting dogs in the seven areas of the United States that were sampled derive from a variant virus that replaced the original strain during 1980.

Animals↗

Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir.

Geographic spread of highly pathogenic avian H5N1 influenza viruses may give rise to an influenza pandemic. During the first months of a pandemic, control measures would rely mainly on antiviral drugs, such as the neuraminidase (NA) inhibitors oseltamivir and zanamivir. In this study, we compare the sensitivities to oseltamivir of the NAs of several highly pathogenic H5N1 viruses isolated in Asia from 1997 to 2005. The corresponding 50% inhibitory concentrations were determined using a standard in vitro NA inhibition assay. The K(m) for the substrate and the affinity for the inhibitor (K(i)) of NA were determined for a 1997 and a 2005 virus, using an NA inhibition assay on cells transiently expressing the viral enzyme. Our data show that the sensitivities of the NAs of H5N1 viruses isolated in 2004 and 2005 to oseltamivir are about 10-fold higher than those of earlier H5N1 viruses or currently circulating H1N1 viruses. Three-dimensional modeling of the N1 protein predicted that Glu248Gly and Tyr252His changes could account for increased sensitivity. Our data indicate that genetic variation in the absence of any drug-selective pressure may result in significant variations in sensitivity to anti-NA drugs. Although the clinical relevance of a 10-fold increase in the sensitivity of NA to oseltamivir needs to be investigated further, the possibility that sensitivity to anti-NA drugs could increase (or possibly decrease) significantly, even in the absence of treatment, underscores the need for continuous evaluation of the impact of genetic drift on this parameter, especially for influenza viruses with pandemic potential.

Antiviral Agents↗

Natural variation of poliovirus neutralization epitopes.

Poliovirus-neutralizing monoclonal antibodies were prepared against type 1, type 2, and type 3 wild laboratory (Mahoney, MEF1, and Saukett) and Sabin vaccine strains. Fifty-five poliovirus laboratory strains and field isolates were assayed by neutralization index test with a panel of homotypic monoclonal antibodies. A total of 27 monoclonal antibodies were used. Two categories of neutralization epitopes were found, i.e., cross-reacting (K), which is present on almost all strains of the same serotype, and strain-specific (V, variable), either wild (VW) or Sabin (VS). Several distinct neutralization epitopes were defined for each of the three poliovirus serotypes in almost every category. The study of antigenic variation of the Sabin type 1 vaccine virus during replication in human intestine showed that the VS neutralization epitope may be lost and even replaced by the VW epitopes of the parental Mahoney virus. A late isolate from a vaccine-fed infant recovered the complete neutralization epitope pattern of the Mahoney strain. Upon in vivo virus replication, a different kind of antigenic variation was also detected in which an epitope lost its function in virus neutralization but kept its antigenic conformation unaltered. Neutralization epitope analysis demonstrated that the presence of VS epitopes on a field isolate suggests the Sabin origin of the strain when the isolate displays the same epitope pattern as the original Sabin virus, or confirms it when the VS epitope(s) is mutually exclusive of VW epitopes. The lack of VS epitopes on a field isolate does not rule out its being of Sabin origin.

Antibodies, Monoclonal↗

Natural variation within the principal adhesion domain of the Plasmodium vivax duffy binding protein.

The blood-stage development of malaria parasites is initiated by the invasion of merozoites into susceptible erythrocytes. Specific receptor-ligand interactions must occur for the merozoites to first attach to and then invade erythrocytes. Because the invasion process is essential for the parasite's survival and the merozoite adhesion molecules are exposed on the merozoite surface during invasion, these adhesion molecules are candidates for antibody-dependent malaria vaccines. The Duffy binding protein of Plasmodium vivax belongs to a family of erythrocyte-binding proteins that contain functionally conserved cysteine-rich regions. The amino cysteine-rich regions of these homologous erythrocyte-binding proteins were recently identified for P. vivax, Plasmodium knowlesi, and Plasmodium falciparum as the principal erythrocyte-binding domains (C. Chitnis and L. H. Miller, J. Exp. Med. 180:497-506, 1994, and B. K. L. Sim, C. E. Chitnis, K. Wasniowska, T. J. Hadley, and L. H. Miller, Science 264:1941-1944, 1994). We report that amino acids in this critical ligand domain of the P. vivax Duffy binding protein are hypervariable, but this variability is limited. Hypervariability of the erythrocyte-binding domain suggests that this domain is the target of an effective immune response, but conservation of amino acid substitutions indicates that functional constraints limit this variation. In addition, the amino cysteine-rich region and part of the hydrophilic region immediately following it were the site of repeated homologous recombinations as represented by tandem repeat sequence polymorphisms. Similar polymorphisms have been identified in the same region of the homologous genes of P. falciparum and P. knowlesi, suggesting that there is a common mechanism of recombination or gene conversion that occurs in these Plasmodium genes.

Amino Acid Sequence↗

Natural variation in the microcystin synthetase operon mcyABC and impact on microcystin production in Microcystis strains.

Toxic Microcystis strains often produce several isoforms of the cyclic hepatotoxin microcystin, and more than 65 isoforms are known. This has been attributed to relaxed substrate specificity of the adenylation domain. Our results show that in addition to this, variability is also caused by genetic variation in the microcystin synthetase genes. Genetic characterization of a region of the adenylation domain in module mcyB1 resulted in identification of two groups of genetic variants in closely related Microcystis strains. Sequence analyses suggested that the genetic variation is due to recombination events between mcyB1 and the corresponding domains in mcyC. Each variant could be correlated to a particular microcystin isoform profile, as identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Among the Microcystis species studied, we found 11 strains containing different variants of the mcyABC gene cluster and 7 strains lacking the genes. Furthermore, there is no concordance between the phylogenies generated with mcyB1, 16S ribosomal DNA, and DNA fingerprinting. Collectively, these results suggest that recombination between imperfect repeats, gene loss, and horizontal gene transfer can explain the distribution and variation within the mcyABC operon.

Amino Acid Sequence↗

Natural variation in translational activities of the 5' nontranslated RNAs of hepatitis C virus genotypes 1a and 1b: evidence for a long-range RNA-RNA interaction outside of the internal ribosomal entry site.

The 5' nontranslated RNA (5'NTR) of a genotype 1b hepatitis C virus (HCV-N) directs cap-independent translation of the HCV-N polyprotein with about twofold less efficiency than the 5'NTR of a genotype 1a virus under physiologic conditions (Hutchinson strain, or HCV-H) (M. Honda et al., Virology 222:31-42, 1996). Here, we show by mutational analysis that substitution of the AG dinucleotide sequence at nucleotides (nt) 34 and 35 of HCV-N with GA (present in HCV-H) restores the translational activity to that of the HCV-H 5'NTR both in vitro and in vivo. These nucleotides are located upstream of the minimal essential internal ribosome entry site (IRES), as a 6-nt deletion spanning nt 32 to 37 also increased the translational activity of the HCV-N 5'NTR to that of HCV-H. Thus, the upstream AG dinucleotide sequence has an inhibitory effect on IRES-directed translation. Surprisingly, however, this inhibitory effect was observed only when the translated, downstream RNA sequence contained nt 408 to 929 of HCV (capsid-coding RNA). Further analysis of RNA transcripts containing frameshift mutations demonstrated that the nucleotide sequence of the transcript, and not the amino acid sequence of the expressed capsid protein, determines this difference in translation efficiency. The difference between the translational activities of the HCV-N and HCV-H transcripts was increased when translation was carried out in reticulocyte lysates containing high K+ concentrations, with a sevenfold difference evident at 130 to 150 mM K+. These results suggest that there is an RNA-RNA interaction involving 5'NTR and capsid-coding sequences flanking the IRES and that this is responsible for the reduced IRES activity of the genotype 1b virus, HCV-N.

5' Untranslated Regions↗