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PubMed2002

Comparison of two aquatic alphaviruses, salmon pancreas disease virus and sleeping disease virus, by using genome sequence analysis, monoclonal reactivity, and cross-infection.

Cell culture isolates of salmon pancreas disease virus (SPDV) of farmed Atlantic salmon and sleeping disease virus (SDV) of rainbow trout were compared. Excluding the poly(A) tracts, the genomic nucleotide sequences of SPDV and SDV RNAs include 11,919 and 11,900 nucleotides, respectively. Phylogenetic analysis places SPDV and SDV between the New World viruses of Venezuelan equine encephalitis virus and Eastern equine encephalitis virus and the Old World viruses of Aura virus and Sindbis virus. When compared to each other, SPDV and SDV show 91.1% nucleotide sequence identity over their complete genomes, with 95 and 93.6% amino acid identities over their nonstructural and structural proteins, respectively. Notable differences between the two viruses include a 24-nucleotide insertion in the C terminus of nsP3 protein of SPDV and amino acid sequence variation at the C termini of the capsid and E1 proteins. Experimental infections of Atlantic salmon and rainbow trout with SPDV and SDV confirmed that the disease lesions induced by SPDV and SDV were similar in nature. Although infections with SPDV and SDV produced similar levels of histopathology in rainbow trout, SDV induced significantly less severe lesions in salmon than did SPDV. Virus neutralization tests performed with sera from experimentally infected salmon indicated that SPDV and SDV belonged to the same serotype; however, antigenic variation was detected among SDV and geographically different SPDV isolates by using monoclonal antibodies. Although SPDV and SDV exhibit minor biological differences, we conclude on the basis of the close genetic similarity that SPDV and SDV are closely related isolates of the same virus species for which the name Salmonid alphavirus is proposed.

Alphavirus↗

PubMed2006

Copy number variation in the genome; the human DMD gene as an example.

Recent developments have yielded new technologies that have greatly simplified the detection of deletions and duplications, i.e., copy number variants (CNVs). These technologies can be used to screen for CNVs in and around specific genomic regions, as well as genome-wide. Several genome-wide studies have demonstrated that CNV in the human genome is widespread and may include millions of nucleotides. One of the questions that emerge is which sequences, structures and/or processes are involved in their generation. Using as an example the human DMD gene, mutations in which cause Duchenne and Becker muscular dystrophy, we review the current data, determine the deletion and duplication profile across the gene and summarize the information that has been collected regarding their origin. In addition we discuss the methods most frequently used for their detection, in particular MAPH and MLPA.

Alleles↗

PubMed2025

The evolution of separate sexes in waterhemp is associated with surprising chromosomal diversity and complexity.

The evolution of separate sexes is hypothesized to occur through distinct pathways involving few large-effect or many small-effect alleles. However, we lack empirical evidence for how these different genetic architectures shape the transition from quantitative variation in sex expression to distinct male and female phenotypes. To explore these processes, we leveraged the recent transition of Amaranthus tuberculatus to dioecy within a predominantly monoecious genus, along with a sex-phenotyped population genomic dataset, and six newly generated chromosome-level haplotype phased assemblies. We identify a ~3 Mb region strongly associated with sex through complementary SNP genotype and sequence-depth-based analyses. Comparative genomics of these proto-sex chromosomes within the species and across the Amaranthus genus demonstrates remarkable variability in their structure and genic content, including numerous polymorphic inversions. No such inversion underlies the extended linkage we observe associated with sex determination. Instead, we identify a complex presence/absence polymorphism reflecting substantial Y-haplotype variation-structured by ancestry, geography, and habitat-but only partially explaining phenotyped sex. Just over 10% of sexed individuals show phenotype-genotype mismatch in the sex-linked region, and along with observation of leakiness in the phenotypic expression of sex, suggest additional modifiers of sex and dynamic gene content within and between the proto-X and Y. Together, this work reveals a complex genetic architecture of sex determination in A. tuberculatus characterized by the maintenance of substantial haplotype diversity, and variation in the expression of sex.

Haplotypes↗

PubMed2005

Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene.

Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (chi(2)=6.9, p<0.03). This result emerged in the whole sample, but was related only to female patients (chi(2)=7.6, p<0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.

Adult↗

PubMed2026

Lifestyle Differentiation Among Marine Denitrifying Microorganisms.

Microorganisms carrying out denitrification in marine anoxic zones drive bioavailable nitrogen loss. Sequencing datasets have demonstrated the modularity of denitrification, with most populations having the genetic capability for only a subset of the pathway (NO3-➔NO2-➔NO➔N2O➔N2). Although previous work provided ecological explanations for this diversity among the functional modules, large trait variations exist within each functional module, and this within-module diversity and its biogeochemical implications remain unexplored. Here, we combine genomic data and modeling to explore how metabolic "lifestyle" strategies influence denitrifier community structure. We build a comprehensive genomic database of marine denitrifiers, and identify lifestyle differentiation among denitrifier functional groups. We then extend a mathematical ecosystem model by resolving two microbial functional types for each module representing a metabolic trade-off: a copiotroph, optimized for fast growth, and an oligotroph, optimized for high nutrient affinity. In the model, as the supply of organic matter relative to nitrate increases, the degree of copiotrophy among the community increases and then decreases. This suggests that oligotrophs are associated with either organic-matter- or nitrate-limiting conditions, whereas copiotrophic lifestyles are associated with an intermediate regime. Our model further associates NO2- reducers with oligotrophy and NO3- reducers with copiotrophy, particularly those producing greenhouse gas nitrous oxide (N2O), linking N2O production to substrate-replete conditions, which is consistent with our genome-based lifestyle estimates. Results provide insight into denitrifier ecological niches and thus the biogeochemical conditions that are associated with the production of intermediates, such as N2O, improving our understanding of how nitrogen cycling will change in a warming ocean.

Marine denitrifiers↗

PubMed1985

Polymorphism of the 3' open reading frame of the virus associated with the acquired immune deficiency syndrome, human T-lymphotropic virus type III.

The genome of the virus associated with the acquired immune deficiency syndrome (AIDS), human T-lymphotropic virus type III (HTLV-III), includes two open reading frames, not found in other retroviruses. One of these, designated 3' open reading frame (3'orf) is 648 base pairs (bp) in length, and overlaps with the 3' long terminal repeat (LTR) sequences. Sequences of additional HTLV-III clones were determined in order to estimate the level and location of variation within 3'orf, to gain some insight into the function of its protein product. Newly determined sequences are reported for 3'orf of two unintegrated clones of HTLV-III and three cDNA clones made from virion RNA derived from the same cell line infected with pooled blood samples of different patients with AIDS or AIDS-related complex symptoms (ARC). In addition, sequences for 3'orf were derived from an unintegrated viral clone derived from a different cell line infected with a distinct isolate from a single patient. These sequences are compared to those previously reported for six other viral clones. Sequences of 3'orf differ among clones by 1.1-10.4% bp and 2.4-17.0% of predicted amino acids. This represents significantly greater sequence variation than is found in the entire genome on average. Moreover, a functional proviral clone has a termination codon at amino acid residue 124 of this open reading frame. This raises questions concerning the structure, and regulation of expression of the protein encoded by 3'orf.

Acquired Immunodeficiency Syndrome↗

PubMed2026

Why Specialized Metabolism Recurrently Emerges in Plants: Chemical and Genomic Biases in Metabolic Diversification.

Specialized metabolism plays a central role in mediating ecological interactions and adaptive responses in plants, while leaving enduring signatures in genome structure and evolution. Here, we synthesize advances in genomics, biochemistry, and evolutionary biology into a metabolite-driven genetic diversification (MGD) framework, in which metabolite chemistry biases the generation, retention, and reuse of genetic variation. When metabolic flux produces reactive, inhibitory, or otherwise costly intermediates, pathways handling these liabilities recurrently recruit gene dosage changes, duplication, and divergence at catalytic and regulatory choke points. These biases do not impose deterministic outcomes; instead, they shape which genomic variants are preferentially sampled and retained under selection, giving rise to predictable patterns of genomic change. Genome multiplication-through whole-genome duplication, allopolyploidy, and cell type-specific endoreduplication-amplifies these effects by altering dosage balance, regulatory context, and retention trajectories. Integrating MGD with genome-scale dosage dynamics explains why specialized metabolism repeatedly converges on similar solutions across plant lineages, even amid extensive genomic turnover and chemical diversity.

Journal Article↗

PubMed1995

Characteristics of ovine and caprine lentivirus infections.

A majority of ovine lentivirus (OvLv) infections seen on farms develop after long incubation and a slow progression of disease to death but in nature they may also have short latency and cause acute leukoencephalitis and/or acute arthritis and pneumonia in young kids or lambs with exceptionally high mortality. Histopathologically, OvLv diseases may be characterized by lymphoid infiltration, lymphoid hyperplasia with germinal centers and plasmocytosis in the lungs and/or in the CNS, joints and udder. Lymphoid hyperplasia in lymph nodes and spleen, as well as lymphoid infiltration in the kidneys, are almost always seen in advanced cases. In some cases, it shows similarities to lymphoproliferative diseases that are considered malignant. Alveolar epithelial hyperplasia in the lungs is generally also seen, especially in older goats with caprine arthritis encephalitis virus (CAEV), and proliferation of these epithelial cells may form acine and papillary structures and in some cases are histopathologically indistinguishable from tumor nodules seen in sheep pulmonary adenomatosis. Because of complexities in the host-lentovirus interaction, cell-associated transmission and extensive antigenic and genomic variation among infecting isolates, control of infection or prevention of spread are problematic by traditional methods and exploration of alternative control strategies employing selection and expansion of animals genetically resistant to OvLv or transgenic for certain viral genes, merits consideration. Interestingly, the pure Awassi sheep breed are susceptible to infection but do not develop the disease, as do European breeds or cross-breeds in Israel, ie they are infected but not diseased. It seems that the local Bedouin black goat breed is resistant to infection of CAEV under natural conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Possible repetitive DNA markers for Eusorghum and Parasorghum and their potential use in examining phylogenetic hypotheses on the origin of Sorghum species.

Genomic structures of two major species in section Eusorghum (Sorghum), Sorghum bicolor and Sorghum halepense, and their phylogenetic relationships with a species in section Parasorghum, Sorghum versicolor, were studied by using cloned repetitive DNA sequences from the three species. Of the five repetitive DNA clones isolated from S. bicolor and S. halepense, four produced qualitatively similar hybridization patterns with detectable variations in copy numbers of some of the restriction fragments on the Southern blots of the two genomic DNAs. One clone was shown to be diagnostic for S. halepense. Molecular analysis at the DNA level indicates that S. bicolor and S. halepense have similar but not identical genomes, consonant with differences in karyotypes, meiotic chromosome behaviors, morphology, and physiology of the species. In addition to five repetitive clones isolated from S. bicolor and S. halepense, eight more sequences were cloned from S. versicolor. Nine clones were found to be specific for either S. bicolor and S. halepense or S. versicolor. The remaining four had a moderate to strong homology with sequences present in all Sorghum species studied. We speculate that the genome in the common ancestor of Sorghum has differentiated to give rise to genomes of at least three major chromosome sizes; large, medium, and small, as seen at present. Amplifications, eliminations, rearrangements, and new syntheses of repetitive sequences may have been involved in genome differentiation of these species. The results also suggest that the S. versicolor genome has strongly diverged from the genomes of the two species in section Eusorghum.

Base Sequence↗

PubMed2026

Comparative Genomics of Paenibacillus Secondary Metabolism: Unveiling the Putative Biosynthetic Gene Cluster for Paenialvins in Paenibacillus Alvei Strain 32.

In this study, we used comparative genomics and culture-based methods to investigate Biosynthetic Gene Clusters (BGCs) responsible for the production of antimicrobial peptides. Paenibacillus alvei strain 32 was isolated from a cystic fibrosis sputum. Its genome was sequenced using Illumina, showing a size of 6,584,590 bp with 239 contigs assembled in 26 scaffolds, an average coverage of 243X, and 6,832 coding sequences. ANI analysis and in silico DNA-DNA hybridization showed its affiliation inside Paenibacillus alvei, with a clear separation from other related strains, leading us to propose a distinct species-level genomic clade (genomospecies) within this group. AntiSMASH analysis predicted 22 putative BGCs in the genome of strain 32. Its culture supernatant exhibited inhibitory activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus, and Enterococcus faecalis. By comparing in silico BGC predictions with activities described in the literature, we propose that strain 32 harbours a specific 110-kb cluster (cluster 6.2) with five non-ribosomal peptide synthetase (NRPS) genes. These synthetases are predicted to direct the assembly of a 16-amino acid backbone that correlates with the structure of paenialvins, which are known anti-MRSA molecules. This study describes the putative biosynthetic pathway of the paenialvins and explains structural variations, bringing useful data on Paenibacillus secondary metabolism for future antibiotic development.

Paenibacillus alvei↗

PubMed2000

Microsatellite variation in populations of Drosophila pseudoobscura and Drosophila persimilis.

We have isolated, characterized and mapped 33 dinucleotide, three trinucleotide and one tetranucleotide repeat loci from the four major chromosomes of Drosophila pseudoobscura. Average inferred repeat unit length of the dinucleotide repeats is 12 repeat units, similar to D. melanogaster. Assays of D. pseudoobscura and populations of its sibling species, D. persimilis, using 10 of these loci show extremely high levels of variation compared with similar studies of dinucleotide repeat variation in D. melanogaster populations. The high levels of variation are consistent with an average mutation rate of approximately 10(-6) per locus per generation and an effective population size of D. pseudoobscura approximately four times larger than that of D. melanogaster. Consistent with allozymes and nucleotide sequence polymorphism, the dinucleotide repeat loci reveal minimal structure across four populations of D. pseudoobscura. Finally, our preliminary recombinational mapping of 24 of these microsatellites suggests that the total recombinational genome size may be larger than previously inferred using morphological mutant markers.

Animals↗

PubMed2026

Malaria-GENOMAP: a web-based tool for exploring genomic variation of malaria parasites.

MOTIVATION: Malaria, caused by Plasmodium parasites, imposes a significant public health burden. While Plasmodium falciparum remains the primary target of elimination strategies due to its high mortality rate, lesser-known species such as P. malariae, P. vivax, and P. knowlesi continue to contribute to substantial human morbidity. Genomic approaches, including whole-genome sequencing, offer powerful tools for understanding the biology, transmission, and emerging drug resistance of these neglected Plasmodium species. However, there is an urgent need for informatic tools to summarize and visualize the high-dimensional and complex genomic data generated. RESULTS: We developed Malaria-GENOMAP, a user-friendly web-based tool, which integrates genomic variant data, such as allele frequencies, with geographical maps and chromosome-wide to gene views for in-depth exploration. The tool includes variation from P. knowlesi (n = 139), P. malariae (n = 158), P. ovale curtisi (n = 36), P. ovale wallikeri (n = 47), P. simium (n = 38), and P. vivax (n = 1359). It enables the investigation of population structure, geographic associations of mutations, and putative drug resistance markers, offering valuable insights for malaria control efforts. AVAILABILITY AND IMPLEMENTATION: Malaria-GENOMAP is available online at https://genomics.lshtm.ac.uk/malaria-genomaps.

Internet↗

PubMed2006

Chromosomal localization of 5S and 18S rDNA in five species of subgenus Strobus and their implications for genome evolution of Pinus.

BACKGROUND AND AIMS: Studying the genome structure of pines has been hindered by their large genomes and uniform karyotypes. Consequently our understanding of the genome organization and evolutionary changes in different groups of pines is extremely limited. However, techniques are now available that can surmount these difficulties. The purpose of this study was to exploit some of these techniques to characterize the genome differentiation between the two subgenera of Pinus: Pinus and Strobus. METHODS: Double-probe fluorescence in-situ hybridization (FISH) was used to localize the 5S and 18S rDNA loci on chromosomes of five species from the subgenus Strobus: P. bungeana, P. koraiensis, P. armandii, P. wallichiana and P. strobus. * KEY RESULTS: The rDNA FISH pattern varied considerably among the five species, with P. bungeana being the most distinct. By comparing the results obtained with those of previous rDNA FISH studies of members of the subgenus Pinus, several general features of rDNA loci distribution in the genus Pinus can be discerned: (a) species of subgenus Strobus generally have more rDNA loci than species of subgenus Pinus, correlating with their larger genomes in the subgenus Strobus; (b) there is a clear differentiation in 5S and 18S rDNA loci linkage patterns between the two subgenera; (c) variations in the rDNA FISH pattern correlate with phylogenetic relationships among species within the subgenus; (d) P. bungeana has fewer 18S rDNA sites than other pines investigated to date, but they give intense signals, and may reflect the primary distribution of the 18S-25S rDNA loci in the genus. CONCLUSIONS: The stable differentiation in rDNA FISH pattern between the subgenera suggests that chromosomal rearrangements played a role in the splitting of the two subgenera, and transpositional events rather than major structural changes are likely responsible for the variable rDNA distribution patterns among species of the same subgenus with conserved karyotypes.

Biological Evolution↗

PubMed2003

From genes to genomes: universal scale-invariant properties of microbial chromosome organisation.

The availability of complete genome sequences for a large variety of organisms is a major advance in understanding genome structure and function. One attribute of genome structure is chromosome organisation in terms of gene localisation and orientation. For example, bacterial operons, i.e. clusters of co-oriented genes that form transcription units, enable functionally related genes to be expressed simultaneously. The description of genome organisation was pioneered with the study of the distribution of genes of the Escherichia coli partial genetic map before the full genome sequence was known. Deploying powerful techniques from circular statistics and signal processing, we revisit the issue of gene localisation and orientation using 89 complete microbial chromosomes from the eubacterial and archaeal domains. We demonstrate that there is no characteristic size pertinent to the description of chromosome structure, e.g. there does not exist any single length appropriate to describe gene clustering. Our results show that, for all 89 chromosomes, gene positions and gene orientations share a common form of scale-invariant correlations known as "long-range correlations" that we can reveal for distances from the gene length, up to the chromosome size. This observation indicates that genes tend to assemble and to co-orient over any scale of observation greater than a few kilobases. This unexpected property of chromosome structure can be portrayed as an operon-like organisation at all scales and implies that a complete scale range extending over more than three orders of magnitudes of chromosome segment lengths is necessary to properly describe prokaryotic genome organisation. We propose that this pattern results from the effects of the superhelical context on gene expression coupled with the structure and dynamics of the nucleoid, possibly accommodating the diverse gene expression profiles needed during the different stages of cellular life.

Archaea↗

PubMed1992

Genetic relatedness of Bradyrhizobium japonicum field isolates as revealed by repeated sequences and various other characteristics.

Forty-nine isolates of Bradyrhizobium japonicum indigenous to a field where soybeans were grown for 45 years without inoculation were characterized by using four DNA hybridization probes from B. japonicum. nifDK-specific hybridization clearly divided the isolates into two divergent groups. Diversity in repeated-sequence (RS)-specific hybridization was observed; 44 isolates derived from 41 nodules were divided into 33 different RS fingerprint groups. Cluster analysis showed that the RS fingerprints were correlated with the nif and hup genotypes. We found multiple bands of RS-specific hybridization for two isolates that differed from the patterns of the other isolates. These results suggest that RS fingerprinting is a valuable tool for evaluating the genetic structure of indigenous B. japonicum populations.

Bacterial Typing Techniques↗

PubMed2001

The VP1-unique region of parvovirus B19: amino acid variability and antigenic stability.

The unique region of structural protein VP1 of parvovirus B19 (erythrovirus B19) is important for eliciting neutralizing antibodies that are responsible for eliminating the virus from the peripheral blood and for inducing lifelong immunity. Neutralizing human MAbs bind a conformationally defined epitope spanning VP1 residues 30-42. The DNA sequence encoding the VP1-unique region was determined in parvovirus B19 isolated from peripheral blood and amniotic fluid of nine acutely infected pregnant women, five arthritis patients and two chronically infected children. The amino acid sequences of the VP1-unique region exhibited higher variability in comparison with other B19-specific proteins. To analyse the influence of amino acid variations on antibody binding and protein conformation, two variants of the VP1-unique region were selected and expressed in E. coli as intein-fusion proteins. The selected variants displayed a number of amino acid exchanges in the VP1-unique region and had mutations in the determined epitope and adjacent regions. After purification via affinity chromatography, the dissociation constants K(D) of VP1-specific human MAbs interacting with the variant antigens and a viral prototype of the VP1-unique region were determined with a quartz crystal microbalance biosensor. A value of 5.4 x 10(-8) M was determined for the prototype isolate pJB; the affinity constants for the variant VP1-unique regions were similar. Comparable values were obtained for interaction of antibodies with non-infectious VP1/VP2 capsids produced by recombinant baculovirus and with B19 virions from amniotic fluid. It is concluded that the conformation of the epitope is unaffected by mutations or the environment of the VP1-unique region in virus capsids.

Amino Acid Sequence↗

PubMed2000

Insertion with long target duplication: a mechanism for gene mobility suggested from comparison of two related bacterial genomes.

The complete genome sequences of two closely related organisms--two Helicobacter pylori strains--have recently become available. Comparison of these genomes at single base pair level has suggested the presence of a mechanism for bacterial gene mobility--insertion with long target duplications. This mechanism is formally similar to classical transposon insertion, but the duplication is much longer, often in the range of 100bp. Restriction and/or modification enzyme genes are often within or adjacent to the insertion. A similar process may have mediated insertion of the cag(+) pathogenicity island in H. pylori. A similar structure was identified in comparisons between Neisseria meningitidis and Neisseria gonorrhoeae genomes. We hypothesize that this mechanism, as well as two other types of polymorphism linked with restriction-modification genes (insertion accompanied by target deletion and a tripartite structure composed of substitution/inversion/deletion), have resulted from attack by restriction enzymes on the chromosome.

Base Sequence↗

PubMed1984

Patterns of DNA structural polymorphism and their evolutionary implications.

The pattern of sites within purified DNA that are highly susceptible to double-stranded cleavage by micrococcal nuclease has been analyzed in the vicinity of over 20 genes from widely separated loci in Drosophila. These genes have uniformly exhibited a distinctive organization of cleavage sites such that at early times of digestion major sites are observed in the spacer regions surrounding the genes, but not within the protein coding regions themselves. Examples examined include Drosophila genes for heat-shock proteins, cytoplasmic actin, ribosomal protein 49, alcohol dehydrogenase, Sgs 4 glue protein, and other developmentally regulated transcripts, a human beta-globin gene, and mouse alpha 3-globin pseudogene. It seems probable that this gene/spacer pattern will be a general one in the genomes of eucaryotes, but not in the genomes of procaryotes, since neither pBR322 nor phage lambda DNA display such a pattern. One observes a nonrandom spacing of strong cleavage sites in Drosophila DNA, with the most frequent intervals being 195 bp and 411 bp. Such a pattern of variation in DNA structure may have evolved to facilitate the packaging of eucaryotic DNA into chromatin.

Animals↗