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At least 307 records · Page 17Linked to original sources
PubMed2002

Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23.

The clinical and biological features of acute myeloid leukemia (AML) with 11q23/MLL translocations are well known, but the characteristics of AML with partial tandem duplication of the MLL gene have not been explored comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA polymerase chain reaction (PCR), reverse-transcription PCR and complementary DNA sequencing. Nine patients showed partial tandem duplication of the MLL gene, including eight (12%) of the 68 with normal karyotype. Seven patients showed fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs 6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had a significantly higher incidence of CD11b expression on leukemic cells than did those without in the subgroup of patients with normal karyotype (75% vs 28%, P = 0.017). There were no significant differences in the expression of lymphoid antigens or other myeloid antigens between the two groups of patients. In adults, the patients with MLL duplication had a shorter median survival time than those without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients. The higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.

Acute Disease↗
PubMed2002

The hidden duplication past of Arabidopsis thaliana.

Analysis of the genome sequence of Arabidopsis thaliana shows that this genome, like that of many other eukaryotic organisms, has undergone large-scale gene duplications or even duplications of the entire genome. However, the high frequency of gene loss after duplication events reduces colinearity and therefore the chance of finding duplicated regions that, at the extreme, no longer share homologous genes. In this study we show that heavily degenerated block duplications that can no longer be recognized by directly comparing two segments because of differential gene loss, can still be detected through indirect comparison with other segments. When these so-called hidden duplications in Arabidopsis are taken into account, many homologous genomic regions can be found in five to eight copies. This finding strongly implies that Arabidopsis has undergone three, but probably no more, rounds of genome duplications. Therefore, adding such hidden blocks to the duplication landscape of Arabidopsis sheds light on the number of polyploidy events that this model plant genome has undergone in its evolutionary past.

Arabidopsis↗
PubMed2025

doubletrouble: an R/Bioconductor package for the identification, classification, and analysis of gene and genome duplications.

SUMMARY: Gene and genome duplications are major evolutionary forces that shape the diversity and complexity of life. However, different duplication modes have distinct impacts on gene function, expression, and regulation. Existing tools for identifying and classifying duplicated genes are either outdated or not user-friendly. Here, we present doubletrouble, an R/Bioconductor package that provides a comprehensive and robust framework for analyzing duplicated genes from genomic data. doubletrouble can detect and classify gene pairs as derived from six duplication modes (segmental, tandem, proximal, retrotransposon-derived, DNA transposon-derived, and dispersed duplications), calculate substitution rates, detect signatures of putative whole-genome duplication events, and visualize results as publication-ready figures. We applied doubletrouble to classify the duplicated gene repertoire in 822 eukaryotic genomes, and results were made available through a user-friendly web interface. AVAILABILITY AND IMPLEMENTATION: doubletrouble is available on Bioconductor (https://bioconductor.org/packages/doubletrouble), and the source code is available in a GitHub repository (https://github.com/almeidasilvaf/doubletrouble). doubletroubledb is available online at https://almeidasilvaf.github.io/doubletroubledb/.

Software↗
PubMed1998

Physical mapping of duplicated genomic regions of two chromosome ends in rice.

Two genomic regions duplicated in distal ends of the short arms of chromosomes 11 and 12 in rice (Oryza sativa L.) were characterized by YAC ordering with 46 genetic markers. Physical maps covering most of the duplicated regions were generated. Thirty-five markers, including 21 rice cDNA clones, showed the duplicated loci arrayed strictly in the same order along the two specific genomic regions. Regardless of their different genetic distances, the two duplicated segments may have a similar and minimum physical size with an expected length of about 2.5 Mb. However, differences of RFLP frequency for the duplicated DNA copies and recombination frequency for a given homoeologous area between the two regions were observed, indicating that these changes in genome organization occurred after the duplication. Our results establish a good model system for resolving the relationships between gene duplication, expression of duplicated genes, and the frequency of meiotic recombination in small chromosomal regions.

Chromosomes, Artificial, Yeast↗
PubMed2003

Duplications of the AZFa region of the human Y chromosome are mediated by homologous recombination between HERVs and are compatible with male fertility.

Deletions of the AZFa region on the long arm of the human Y chromosome cause male infertility. Previous work has shown that this is an example of a genomic disorder, since most deletions are caused by non-allelic homologous recombination between endogenous retroviral elements (HERVs) flanking the 780 kb region. The reciprocal products of these deletion events, AZFa duplications, have not been reported to date. Here we show that duplication chromosomes exist in population samples by detecting Y-chromosomal short tandem repeat (YSTR) allele duplications within the AZFa region, and by showing that two chromosomes carrying these duplicated alleles contain a third junction-specific HERV sequence. Sequence analysis of these cases, which most likely represent independent duplication events, shows that breakpoints lie in the same region of inter-HERV sequence identity as do deletion breakpoints, and thus that the mechanism of duplication is indeed the reciprocal of deletion. Consideration of the accumulated Y-STR allele diversity between duplicated copies of the AZFa region indicates that one of the duplication chromosomes has been in the population for at least 17 generations, and therefore must be compatible with male fertility.

Base Sequence↗
PubMed2026

Adaptive deletion of functional duplicate genes in Drosophila.

Gene deletion is traditionally viewed as a nonadaptive mechanism that eliminates functional redundancy, yet emerging evidence indicates that it disproportionately affects tissue-specific duplicates with unique functions. Here, we test whether gene deletion preferentially removes weakly constrained, degenerating duplicates or instead eliminates functionally active duplicates through an adaptive process. To identify the evolutionary and functional factors that determine which duplicates are lost, we systematically analyzed 100 gene deletion events in Drosophila by integrating sequence, expression, interaction, and structural data. We uncovered a strong bias toward the loss of younger child copies among functionally unique duplicates, whereas no such bias was observed for redundant duplicates. Contrary to expectations under relaxed constraint, deleted functionally unique genes evolve more slowly, show higher expression, engage in more protein-protein interactions, and do not exhibit elevated structural divergence or intrinsic disorder relative to redundant duplicates. When compared with single-copy genes, deleted functionally unique genes display similar evolutionary rates, slightly lower expression, greater network connectivity, comparable structural divergence, and lower intrinsic disorder. These patterns suggest that deletion frequently affects functionally active rather than degenerate genes. Collectively, our results support the hypothesis that gene deletion in Drosophila can represent an adaptive process acting on transiently functional duplicates, potentially driven by either genome streamlining or context-dependent deleterious effects.

evolution↗
PubMed2004

Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes.

With about 24,000 extant species, teleosts are the largest group of vertebrates. They constitute more than 99% of the ray-finned fishes (Actinopterygii) that diverged from the lobe-finned fish lineage (Sarcopterygii) about 450 MYA. Although the role of genome duplication in the evolution of vertebrates is now established, its role in structuring the teleost genomes has been controversial. At least two hypotheses have been proposed: a whole-genome duplication in an ancient ray-finned fish and independent gene duplications in different lineages. These hypotheses are, however, based on small data sets and lack adequate statistical and phylogenetic support. In this study, we have made a systematic comparison of the draft genome sequences of Fugu and humans to identify paralogous chromosomal regions ("paralogons") in the Fugu that arose in the ray-finned fish lineage ("fish-specific"). We identified duplicate genes in the Fugu by phylogenetic analyses of the Fugu, human, and invertebrate sequences. Our analyses provide evidence for 425 fish-specific duplicate genes in the Fugu and show that at least 6.6% of the genome is represented by fish-specific paralogons. We estimated the ages of Fugu duplicate genes and paralogons using the molecular clock. Remarkably, the ages of duplicate genes and paralogons are clustered, with a peak around 350 MYA. These data strongly suggest a whole-genome duplication event early during the evolution of ray-finned fishes, probably before the origin of teleosts.

Animals↗
PubMed2005

Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. What is the role of genome duplication in the evolution of complexity and diversity?

Gene and genome duplications provide a source of genetic material for mutation, drift, and selection to act upon, making new evolutionary opportunities possible. As a result, many have argued that genome duplication is a dominant factor in the evolution of complexity and diversity. However, a clear correlation between a genome duplication event and increased complexity and diversity is not apparent, and there are inconsistencies in the patterns of diversity invoked to support this claim. Interestingly, several estimates of genome duplication events in vertebrates are preceded by multiple extinct lineages, resulting in preduplication gaps in extant taxa. Here we argue that gen(om)e duplication could contribute to reduced risk of extinction via functional redundancy, mutational robustness, increased rates of evolution, and adaptation. The timeline for these processes to unfold would not predict immediate increases in species diversity after the duplication event. Rather, reduced probabilities of extinction would predict a latent period between a genome duplication and its effect on species diversity or complexity. In this paper, we will develop the idea that genome duplication could contribute to species diversity through reduced probability of extinction.

Animals↗
PubMed2006

Gene loss and evolutionary rates following whole-genome duplication in teleost fishes.

Teleost fishes provide the first unambiguous support for ancient whole-genome duplication in an animal lineage. Studies in yeast or plants have shown that the effects of such duplications can be mediated by a complex pattern of gene retention and changes in evolutionary pressure. To explore such patterns in fishes, we have determined by phylogenetic analysis the evolutionary origin of 675 Tetraodon duplicated genes assigned to chromosomes, using additional data from other species of actinopterygian fishes. The subset of genes, which was retained in double after the genome duplication, is enriched in development, signaling, behavior, and regulation functional categories. The evolutionary rate of duplicate fish genes appears to be determined by 3 forces: 1) fish proteins evolve faster than mammalian orthologs; 2) the genes kept in double after genome duplication represent the subset under strongest purifying selection; and 3) following duplication, there is an asymmetric acceleration of evolutionary rate in one of the paralogs. These results show that similar mechanisms are at work in fishes as in yeast or plants and provide a framework for future investigation of the consequences of duplication in fishes and other animals.

Animals↗
PubMed2002

Reconstructing the duplication history of tandemly repeated genes.

We present a novel approach to deal with the problem of reconstructing the duplication history of tandemly repeated genes that are supposed to have arisen from unequal recombination. We first describe the mathematical model of evolution by tandem duplication and introduce duplication histories and duplication trees. We then provide a simple recursive algorithm which determines whether or not a given rooted phylogeny can be a duplication history and another algorithm that simulates the unequal recombination process and searches for the best duplication trees according to the maximum parsimony criterion. We use real data sets of human immunoglobulins and T-cell receptors to validate our methods and algorithms. Identity between most parsimonious duplication trees and most parsimonious phylogenies for the same data, combined with the agreement with additional knowledge about the sequences, such as the presence of polymorphisms, shows strong evidence that our reconstruction procedure provides good insights into the duplication histories of these loci.

Algorithms↗
PubMed2003

Duplicate publications in the otolaryngology literature.

OBJECTIVE/HYPOTHESIS: A duplicate publication duplicates other published work by the same author(s). The purpose of the study was to define the extent of this problem within the otolaryngology literature. STUDY DESIGN: Retrospective review of the literature. METHODS: Original articles published in Archives of Otolaryngology-Head and Neck Surgery and Laryngoscope in 1999 were reviewed using the OVID search engine. Titles and abstracts from English articles written by the same first, second, or last author were analyzed, and suspected publications were evaluated. Duplicate publications were classified as dual (identical data set and conclusions) or suspected dual (nearly identical data set and conclusions) publications. RESULTS: Of the 492 articles evaluated, 40 index articles were identified. These led to a total of 42 (8.5%) duplicate articles of which 27 were classified as dual and 15 as suspected dual publications. Approximately half of the duplicate publications were published by authors in the United States (55%). Duplicate articles usually appeared within 12 months of the each other (74%) and failed to cross-reference the earlier publication (83%). CONCLUSIONS: Journal editors have become aware of an increase in the number of duplicate publications in the medical literature. The incidence of duplicate publications in the otolaryngology literature appears to be similar to that in other specialties.

Duplicate Publications as Topic↗
PubMed2001

Comparative genomics provides evidence for an ancient genome duplication event in fish.

There are approximately 25 000 species in the division Teleostei and most are believed to have arisen during a relatively short period of time ca. 200 Myr ago. The discovery of 'extra' Hox gene clusters in zebrafish (Danio rerio), medaka (Oryzias latipes), and pufferfish (Fugu rubripes), has led to the hypothesis that genome duplication provided the genetic raw material necessary for the teleost radiation. We identified 27 groups of orthologous genes which included one gene from man, mouse and chicken, one or two genes from tetraploid Xenopus and two genes from zebrafish. A genome duplication in the ancestor of teleost fishes is the most parsimonious explanation for the observations that for 15 of these genes, the two zebrafish orthologues are sister sequences in phylogenies that otherwise match the expected organismal tree, the zebrafish gene pairs appear to have been formed at approximately the same time, and are unlinked. Phylogenies of nine genes differ a little from the tree predicted by the fish-specific genome duplication hypothesis: one tree shows a sister sequence relationship for the zebrafish genes but differs slightly from the expected organismal tree and in eight trees, one zebrafish gene is the sister sequence to a clade which includes the second zebrafish gene and orthologues from Xenopus, chicken, mouse and man. For these nine gene trees, deviations from the predictions of the fish-specific genome duplication hypothesis are poorly supported. The two zebrafish orthologues for each of the three remaining genes are tightly linked and are, therefore, unlikely to have been formed during a genome duplication event. We estimated that the unlinked duplicated zebrafish genes are between 300 and 450 Myr. Thus, genome duplication could have provided the genetic raw material for teleost radiation. Alternatively, the loss of different duplicates in different populations (i.e. 'divergent resolution') may have promoted speciation in ancient teleost populations.

Animals↗
PubMed2001

Gene duplication and the structure of eukaryotic genomes.

A simple method for understanding how gene duplication has contributed to genomic structure was applied to the complete genomes of Caenorhabditis elegans, Drosophila melanogaster, and yeast Saccharomyces cerevisiae. By this method, the genes belonging to gene families (the paranome) were identified, and the extent of sharing of two or more families between genomic windows was compared with that expected under a null model. The results showed significant evidence of duplication of genomic blocks in both C. elegans and yeast. In C. elegans, the five block duplications identified all occurred intra-chromosomally, and all but one occurred quite recently. In yeast, by contrast, 39 duplicated blocks were identified, and all but one of these was inter-chromosomal. Of these 39 blocks, 28 showed evidence of ancient duplication, possibly as a result of an ancient polyploidization event. By contrast, three blocks showed evidence of very recent duplication, while seven others showed a mixture of ancient and recent duplication events. Thus, duplication of genomic blocks has been an ongoing feature of yeast evolution over the past 200--300 million years.

Animals↗
PubMed2004

Analysis of segmental duplications and genome assembly in the mouse.

Limited comparative studies suggest that the human genome is particularly enriched for recent segmental duplications. The extent of segmental duplications in other mammalian genomes is unknown and confounded by methodological differences in genome assembly. Here, we present a detailed analysis of recent duplication content within the mouse genome using a whole-genome assembly comparison method and a novel assembly independent method, designed to take advantage of the reduced allelic variation of the C57BL/6J strain. We conservatively estimate that approximately 57% of all highly identical segmental duplications (>or=90%) were misassembled or collapsed within the working draft WGS assembly. The WGS approach often leaves duplications fragmented and unassigned to a chromosome when compared with the clone-ordered-based approach. Our preliminary analysis suggests that 1.7%-2.0% of the mouse genome is part of recent large segmental duplications (about half of what is observed for the human genome). We have constructed a mouse segmental duplication database to aid in the characterization of these regions and their integration into the final mouse genome assembly. This work suggests significant biological differences in the architecture of recent segmental duplications between human and mouse. In addition, our unique method provides the means for improving whole-genome shotgun sequence assembly of mouse and future mammalian genomes.

Animals↗
PubMed2004

Recovery of a function involving gene duplication by retroposition in Saccharomyces cerevisiae.

The duplication of DNA sequences contributes to genomic plasticity and is known to be one of the key factors responsible for evolution. The mechanisms underlying these rare events, which have been frequently mentioned by authors performing genomic analysis, have not yet been completely elucidated. These mechanisms were approached here in the yeast Saccharomyces cerevisiae, using a positive selection screen based on a particular mutated allele of the URA2 gene. Spontaneous revertants containing a duplication of the terminal part of the URA2 gene were selected and analyzed. Some important features of the duplicated regions, such as their chromosome location, size, and insertion sites, were characterized. The events selected correspond to a single inter- or intrachromosomal gene duplication process. The duplicated ATCase sequence is generally punctuated by a poly(A) tract and is always located in Ty1 sequences. In addition, the activation of a Ty1 transcription process increased the frequency of the duplication events. All in all, these data suggest that the duplication mechanism involves the reverse transcription of mRNA and the subsequent integration of the cDNA into a Ty1 area. The Ty1 elements and the retrotransposon-encoded function are key factors contributing to chromosomal reshaping. The genomic rearrangements described constitute experimental evidence for the recovery of a function involving duplication by retroposition.

3' Flanking Region↗
PubMed2005

The evolutionary fate of MULE-mediated duplications of host gene fragments in rice.

DNA transposons are known to frequently capture duplicated fragments of host genes. The evolutionary impact of this phenomenon depends on how frequently the fragments retain protein-coding function as opposed to becoming pseudogenes. Gene fragment duplication by Mutator-like elements (MULEs) has previously been documented in maize, Arabidopsis, and rice. Here we present a rigorous genome-wide analysis of MULEs in the model plant Oryza sativa (domesticated rice). We identify 8274 MULEs with intact termini and target-site duplications (TSDs) and show that 1337 of them contain duplicated host gene fragments. Through a detailed examination of the 5% of duplicated gene fragments that are transcribed, we demonstrate that virtually all cases contain pseudogenic features such as fragmented conserved protein domains, frameshifts, and premature stop codons. In addition, we show that the distribution of the ratio of nonsynonymous to synonymous amino acid substitution rates for the duplications agrees with the expected distribution for pseudogenes. We conclude that MULE-mediated host gene duplication results in the formation of pseudogenes, not novel functional protein-coding genes; however, the transcribed duplications possess characteristics consistent with a potential role in the regulation of host gene expression.

DNA Transposable Elements↗
PubMed2006

Widespread genome duplications throughout the history of flowering plants.

Genomic comparisons provide evidence for ancient genome-wide duplications in a diverse array of animals and plants. We developed a birth-death model to identify evidence for genome duplication in EST data, and applied a mixture model to estimate the age distribution of paralogous pairs identified in EST sets for species representing the basal-most extant flowering plant lineages. We found evidence for episodes of ancient genome-wide duplications in the basal angiosperm lineages including Nuphar advena (yellow water lily: Nymphaeaceae) and the magnoliids Persea americana (avocado: Lauraceae), Liriodendron tulipifera (tulip poplar: Magnoliaceae), and Saruma henryi (Aristolochiaceae). In addition, we detected independent genome duplications in the basal eudicot Eschscholzia californica (California poppy: Papaveraceae) and the basal monocot Acorus americanus (Acoraceae), both of which were distinct from duplications documented for ancestral grass (Poaceae) and core eudicot lineages. Among gymnosperms, we found equivocal evidence for ancient polyploidy in Welwitschia mirabilis (Gnetales) and no evidence for polyploidy in pine, although gymnosperms generally have much larger genomes than the angiosperms investigated. Cross-species sequence divergence estimates suggest that synonymous substitution rates in the basal angiosperms are less than half those previously reported for core eudicots and members of Poaceae. These lower substitution rates permit inference of older duplication events. We hypothesize that evidence of an ancient duplication observed in the Nuphar data may represent a genome duplication in the common ancestor of all or most extant angiosperms, except Amborella.

Cycadopsida↗
PubMed2003

Pericentromeric duplications in the laboratory mouse.

Duplications have long been postulated to be an important mechanism by which genomes evolve. Interspecies genomic comparisons are one method by which the origin and molecular mechanism of duplications can be inferred. By comparative mapping in human, mouse, and rat, we previously found evidence for a recent chromosome-fission event that occurred in the mouse lineage. Cytogenetic mapping revealed that the genomic segments flanking the fission site appeared to be duplicated, with copies residing near the centromere of multiple mouse chromosomes. Here we report the mapping and sequencing of the regions of mouse chromosomes 5 and 6 involved in this chromosome-fission event as well as the results of comparative sequence analysis with the orthologous human and rat genomic regions. Our data indicate that the duplications associated with mouse chromosomes 5 and 6 are recent and that the resulting duplicated segments share significant sequence similarity with a series of regions near the centromeres of the mouse chromosomes previously identified by cytogenetic mapping. We also identified pericentromeric duplicated segments shared between mouse chromosomes 5 and 1. Finally, novel mouse satellite sequences as well as putative chimeric transcripts were found to be associated with the duplicated segments. Together, these findings demonstrate that pericentromeric duplications are not restricted to primates and may be a common mechanism for genome evolution in mammals.

Animals↗