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At least 19 recordsLinked to original sources
PubMed2025

SegMantX: A Novel Tool for Detecting DNA Duplications Uncovers Prevalent Duplications in Plasmids.

Segmental duplications play an important role in genome evolution via their contribution to copy-number variation, gene-family diversification, and the emergence of novel functions. The detection of segmental duplications is challenging due to heterogeneous amelioration of sequence similarity among duplicates, which hinders the reconstruction of continuous sequence alignment. Here we introduce SegMantX, a novel approach for the identification of diverged segmental duplications in prokaryote genomes using local alignment chaining. In this approach, local alignments resulting from a preliminary sequence similarity search (e.g. BLASTn) are chained into continuous segments. Evaluating the performance of SegMantX using simulated sequences shows that the tool can detect diverged duplications beyond the sensitivity limits of standard alignment-based methods. Applying SegMantX to 6,784 enterobacterial plasmids, we find that 65% plasmids contain duplicated regions and gene duplications, most of which correspond either to dispersed, noncoding regions or duplicated mobile genetic elements (MGEs; e.g. transposons and insertion sequences). Furthermore, we demonstrate the applicability of SegMantX for the identification of diverged gene transfers between replicons and plasmid hybridization events. Our findings highlight MGEs as drivers of segmental duplications in plasmid evolution, leading to the amplification of their cargo genes, including antibiotic resistance genes. SegMantX provides a powerful framework for reconstructing diverged segmental duplications and other alignment problems.

Plasmids↗
PubMed2025

Rethinking the pathogenicity of intragenic DMD duplications detected by carrier screening: High prevalence of nontandem duplications revealed by long-read sequencing.

PURPOSE: The pathogenicity of intragenic duplications depends on their structural configuration. Tandem duplications often disrupt reading frames and cause gene loss of function, whereas interspersed (nontandem) duplications are largely benign. When the configuration cannot be determined, current guidelines presume a tandem structure, leading to some laboratories automatically classifying such variants as likely pathogenic or pathogenic. This study evaluates the validity of this presumption for DMD, in patients with and without clinical indications of dystrophinopathy. METHODS: We performed high-coverage long-read genome sequencing on 15 patients with intragenic DMD duplications. A total of 4 patients had clinically indicated dystrophinopathy testing, whereas in the remaining 11 patients, the duplications were detected without clear indications of dystrophinopathy (eg, through carrier screening). RESULTS: All 4 patients with clinical indications had tandem duplications. In contrast, 64% (7/11) of the cases without such indications had interspersed duplications, with 4 subsequently reclassified as likely benign, 2 (likely) pathogenic, and 1 uncertain. These duplications were often complex, involving coduplications or codeletions with other regions. CONCLUSION: Our findings challenge the presumption that intragenic DMD duplications are predominantly in tandem. This highlights the need for a cautious variant interpretation approach, particularly in carrier screening and other settings in which variants are identified without indications of dystrophinopathy.

Humans↗
PubMed1978

Gene duplication in tetraploid fish: model for gene silencing at unlinked duplicated loci.

Several groups of fishes, including salmonids and catastomids, appear to have originated through genome duplication events. However, these two groups retain approximately 50% of the loci examined as functioning duplicates, despite the passage of 50 million years or more of mutation and selection. Although other effects are not excluded, this apparently slow rate of duplicate silencing can be explained in terms of the effects of selection against defective double homozygotes to unlinked duplicates. We have derived a computer simulation of genetic drift that affords direct evaluation of the effects of population size (N), mutation rate (micron), initial allele frequencies, back mutation, fitness, and time on the probability of fixation for null alleles at unlinked duplicate loci. The results show that this probability is approximately linearly related to population size for N greater than or equal to 10(3). Specifically, for naive populations, the time for 50% probability of gene silencing is approximately equal to 15N + micron-3/4 generations. The retention of 50% of the loci as functional duplicates may therefore result from the large effective size of salmonid and catastomid populations. The results also show that, under most conditions for populations of 2000--3000 or larger, unlinked duplicate loci will be sustained in the functional state longer than tandem (linked) duplicates and hence are available for evolution of new functions for a longer time.

Alleles↗
PubMed1978

Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium. I. Induction of duplications.

In Salmonella typhimurium a simple selection has been described to detect bacteria that are merodiploid for almost one-third of the chromosome. The selective procedure is based upon improved utilization of L-malate as the sole carbon source in merodiploid strains. The spontaneous frequency of the duplication in haploid strains is approximately 10(-4) per cell plated. Following the exposure of a haploid strain to mutagenic agents, there is a dose-dependent increase in the duplication frequency above the spontaneous level. In this paper we describe the induction of genetic duplications in Salmonella typhimurium by X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), nitrous acid, and the azaacridine half mustard, ICR-372.

Acridines↗
PubMed1977

Duplication variables related to partial denture castings. 1. The duplicating flask.

A metal die simulating a model of a partially dentate upper jaw prepared with milled facets for reference measurement with vernier calipers was used for the making of duplicate stone models, in three different duplicating flasks. The observation showed that irrespective of the flask size, the duplicated models were slightly wider.

Dental Casting Technique↗
PubMed1977

Gene duplication in salmonid fishes: evidence for duplicated but catalytically equivalent A4 lactate dehydrogenases.

Skeletal muscle tissues from many species of salmonid fish are known to exhibit a set of three of five isozymes for A4-type lactate dehydrogenase (L-lactate: NAD oxidoreductase, E.C. 1.1.1.27), but the genetic basis for this isozyme system has not previously been assessed. This isozyme system was purified to homogeneity from salmon (Oncorhynchus tshawytscha) and shown to be composed of two polypeptides. Aalpha and Abeta, in binomial tetrameric combinations. Amino acid analysis revealed that Aalpha and Abeta are closely related but genetically distinct proteins, and thus are coded for the recently duplicated structural loci. Catalytic studies on the purified intact salmon isozyme system and on the isozymically pure Aalpha4 and Abeta4 homotetramers from brown trout (Salmo trutta) revealed no significant differences in catalytic properties among these enzymes, suggesting equivalent catalytic function of Aalpha and Abeta. These results, in combination with studies on polypeptide and isozyme ratios, suggest that one of the duplicated loci in salmon may be drifting toward a nonfunctional state by accumulation of mutations in regulatory DNA rather than in the structural gene itself.

Amino Acid Sequence↗
PubMed1978

Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium. II. Stimulation of duplication-loss from merodiploids.

Strains of Salmonella typhimurium which contain a duplication of approximately 30% of the genome may be obtained by a simple selective procedure. These strains are highly unstable, losing the duplication when grown on non-selective medium. In this paper we report that treatment of merodiploid bacteria with mutagenic agents stimulates the rate at which haploid segregants are obtained from merodiploid strains. The mutagens which have been tested for this effect are X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), and the azaacridine half-mustard ICR-372.

Aza Compounds↗
PubMed1977

Partial duplication 5q syndrome: phenotypic similarity in two sisters with identical karyotype (partial duplication 5q33 leads to 5qter and partial deficiency 8p23 leads to pter).

Two sisters with statomotor developmental retardation microcephaly, hydrocephalus internus and externus without signs of pressure, heart defect (ventricular septal defect), early pulmonary resistance and characteristic facial changes were found to have the same unbalanced karyotype with partial trisomy 5q3300 leads to 5qter and partial monosomy 8p2300 leads to 8pter, derived from a balanced reciprocal paternal translocation: 46,XY,t(5;8)(q3300;p2300). The older girl was tested for the erythrocyte enzyme glutathion reductase. She had normal values.

Abnormalities, Multiple↗
PubMed1976

The genetic instability and mutagenic interaction of chromosomal duplications present together in haploid strains of Aspergillus nidulans.

Previous work has shown that strains of Aspergillus nidulans with a chromosome segment in duplicate (one in normal position, one translocated to another chromosome) are unstable. Deletions occur from either duplicate segment. The present work has shown that when a chromosome I duplication and a chromosome III duplication are together in a haploid, deletions from the intact III duplication generally precede deletions from particular sections of the I duplication. Furthermore, the III duplication can enhance to some (but not major) extent the frequency of deletions from the I duplication. After the III duplication becomes reduced in size as a result of the loss of chromosomal material from the translocated duplicate III segment, such a reduced III duplication can greatly enhance the frequency of deletions from the I duplication. In other words, a III duplication of reduced size can promote far more deletions from the I duplication than the intact III duplication. The major increase in the deletional instability of the I duplication as promoted by the reduced III duplication is confined to the translocated duplicate I segment. The reduced III duplication can induce deletions from a section of the translocated duplicate I segment in accord with a temporal programme, and it appears that a particular region of the I duplication is far more under the mutagenic influence of the reduced III duplication than another region. Moreover, there is indication that there is a differential effect of two generally different genetic backgrounds on the susceptibility of duplication-regions to deletion. Possible mechanisms involved in such chromosomal instability are proposed. A manner in which genetic instability may be related to development is also proposed.

Aspergillus nidulans↗
PubMed1975

Heterokaryon incompatibility genes in Neurospora crassa detected using duplication-producing chromosome rearrangements.

Evidence is presented for five or six previously undetected heterokaryon incompatibility (het) loci, bringing to about ten the number of such genes known in Neurospora crassa. The genes were detected using chromosome duplications (partial diploids), on the basis of properties previously known for het genes in duplications. Duplications homozygous for het genes are usually normal in growth and morphology, whereas those heterozygous are strikingly different. The heterozygotes are inhibited in their initial growth, produce brown pigment on appropriate medium, and later "escape" from their inhibition, as a result of somatic events, to produce wild-type growth. - Five normal-sequence strains were crossed to 14 duplication-producing chromosome rearrangements, and the duplication progeny were examined for properties characteristic of duplications heterozygous for known het genes. Each cross produced duplications for a specific region of the genome, depending on the rearrangement. Normal-sequence strains were wild types from nature, chosen from diverse geographic locations to serve as sources of genetic variation. - The duplication method was very effective. Most of the longer duplications uncovered het genes. The genes are: het-5 (on linkage group IR, in the region covered by duplications produced using rearrangement T (IR LEADS TO VIR)NM103), het-6 (on IIL, covered by T(IIL LEADS TO VI)P2869 and T(IIL LEADS TO IIIR)AR18 duplications), het-7 (tentatively assigned to IIIR, T(IIIR LEADS TO VIL)D305), het-8 (VIL, T(VIL LEADS TO IR)T39M777), het-9 (VIR LEADS TO IVR)AR209), and het-10 (VIIR, T(VIIR LEADS TO IL)5936.

Cell Nucleus↗
PubMed2025

Gene and Genome Duplication in Spiders.

Gene and genome duplications are widely observed across various organisms, including plants, yeasts, and animals. Numerous studies link gene duplications to the emergence of novel phenotypes, supporting the hypothesis that duplication events are advantageous for adaptive evolution. Whole-genome duplications (WGD) are especially prevalent in plants and have also occurred ancestrally in vertebrates. However, large-scale duplication events in other animal groups remain understudied, partly due to limited genomic resources. Arthropods, particularly insects, represent one of the most diverse animal clades in terms of both species and phenotypic diversity. With increasing availability of chromosome-level genomes, large-scale duplications appear to be rare in insects but are more frequent in chelicerates (e.g. spiders, scorpions, and horseshoe crabs). This makes chelicerates an intriguing group for comparing the mechanisms, fates, and evolutionary impacts of large-scale duplications with those seen in plants and vertebrates. In this review, we synthesize and discuss current research on WGD in spiders and discuss different scenarios for genes following gene duplication events (conservation, nonfunctionalization, subfunctionalization, specialization, drift, neofunctionalization) in the context of experimental studies. We hypothesize if there might be common trajectories after duplication and how these could be tested.

Animals↗