Drosophila P element transposase induces male recombination additively and without a requirement for P element excision or insertion.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 1013-1023 ◽  
Author(s):  
M McCarron ◽  
A Duttaroy ◽  
G Doughty ◽  
A Chovnick

Abstract P element dysgenesis-associated male recombination in Drosophila was examined with a selective system focused upon a section of the third chromosome divided into eight recombination segments. Tests compared crossing over in the presence of none, one and two doses of P(delta 2-3)(99B), a non-mobile transposase source, in the absence of a mobilizable P element target in the genome. In the presence of the P transposase source, and without a P element target, significant male recombination occurred in genomic regions physically separated from the P(delta 2-3) site. Using two doses of P(delta 2-3) without a P element target, the male recombination rate doubled, and 90% of the crossovers occurred in the pericentric region. The distribution of recombination events, in the absence of P element targets approximates that seen in studies of radiation induced mitotic crossing over and the metaphase chromosome map. Another experiment examined the effects of one dose of P(delta 2-3) on a genome with a single P element target, P(lArB)(87C9), in the third recombination segment. Crossovers increased 58-fold in the immediate region of the P element target.

Genetics ◽  
1990 ◽  
Vol 124 (2) ◽  
pp. 317-329
Author(s):  
A Duttaroy ◽  
M McCarron ◽  
K Sitaraman ◽  
G Doughty ◽  
A Chovnick

Abstract P element dysgenesis associated male recombination in Drosophila was examined with a selective system focused upon 5% of the standard female genetic map divided into eight recombination segments. We found no correspondence between P element mobilization events and recombination in males in the intervals monitored. We defined two adjacent short genetic and molecular regions, one devoid of male recombination and the other acting as a "hot spot" for exchange in the absence of supporting P element insertion and excision activity. These data suggest that, even in the presence of mobilizing P elements, transposase may be active at non-P element sites, and that the genome may harbor sequences ranging from highly responsive to completely unresponsive to transposase action. A viewpoint is presented wherein P elements, with sequences that bind transposase, serve to focus the recombination action of transposase to encompass a region of DNA radiating outward from the initial binding site. We suggest that this region is measured in terms of chromosomal segments rather than limited to P element sequences.


1989 ◽  
Vol 54 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Margaret Y. McCarron ◽  
Atanu Duttaroy ◽  
Glenn A. Doughty ◽  
Arthur Chovnick

SummaryMale recombination in P–M dysgenic crosses has been viewed as a reflection of P-element transposase interacting with P elements. However, recent studies suggest that the transposase may catalyse double-stranded breaks in chromosomal DNA. We have, therefore, introduced P(Δ2–3 ry+) (99B), a single non-mobile P-element transposase source, into the long-standing laboratory true M strains of a flanking lethal crossover selective system, thus facilitating the examination of rare male recombination events as an assay for transposase activity. We find that the rate of male recombination in the presence of this non-mobile P element is greater than twenty times the background rate of male recombination in the control examined prior to introduction of the transposase source.


1989 ◽  
Vol 53 (3) ◽  
pp. 163-171 ◽  
Author(s):  
K. A. Exley ◽  
P. Eggleston

SummaryThe frequency and distribution of P elements were investigated in the third chromosomes of two wild-type strains of Drosophila melanogaster using in situ hybridization of biotinylated probes to the polytene chromosomes. The relationship between these data and the extent of hybrid dysgenesis was determined through assays of egg production, egg hatchability (F2 embryo lethality), snw destabilization and male recombination along the third chromosome. The results suggest that P-element distribution, frequency and structure are all contributory factors in the regulation of hybrid dysgenesis. Texas 6 was shown consistently to be a stronger P strain than Texas 1, eliciting greater reductions in fertility, more extensive snw destabilization and higher frequencies of male recombination. Clustering of male recombination events, arising from pre-meiotic crossing over, was evident among the dysgenic progeny of each strain. Male recombination and snw destabilization were independently distributed among the dysgenic males studied, suggesting that these traits represent separate P-mediated functions. The third chromosome male recombination maps produced by the two strains differed significantly from each other and from the published female meiotic and polytene chromosome maps. Male recombination breakpoints were associated with the original distribution of P sequences in the two strains and the results suggest that this relationship may be closer for potentially complete P factors than for P sequences in general. An analysis of sub-lines derived from individual recombinant males revealed that chromosomal breakpoints could also be associated with novel insertions following P-element transposition.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1984
Author(s):  
Majid Nikpay ◽  
Sepehr Ravati ◽  
Robert Dent ◽  
Ruth McPherson

Here, we performed a genome-wide search for methylation sites that contribute to the risk of obesity. We integrated methylation quantitative trait locus (mQTL) data with BMI GWAS information through a SNP-based multiomics approach to identify genomic regions where mQTLs for a methylation site co-localize with obesity risk SNPs. We then tested whether the identified site contributed to BMI through Mendelian randomization. We identified multiple methylation sites causally contributing to the risk of obesity. We validated these findings through a replication stage. By integrating expression quantitative trait locus (eQTL) data, we noted that lower methylation at cg21178254 site upstream of CCNL1 contributes to obesity by increasing the expression of this gene. Higher methylation at cg02814054 increases the risk of obesity by lowering the expression of MAST3, whereas lower methylation at cg06028605 contributes to obesity by decreasing the expression of SLC5A11. Finally, we noted that rare variants within 2p23.3 impact obesity by making the cg01884057 site more susceptible to methylation, which consequently lowers the expression of POMC, ADCY3 and DNAJC27. In this study, we identify methylation sites associated with the risk of obesity and reveal the mechanism whereby a number of these sites exert their effects. This study provides a framework to perform an omics-wide association study for a phenotype and to understand the mechanism whereby a rare variant causes a disease.


Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1585-1593 ◽  
Author(s):  
Wolfgang Stephan ◽  
Charles H Langley

Abstract Surveys in Drosophila have consistently found reduced levels of DNA sequence polymorphism in genomic regions experiencing low crossing-over per physical length, while these same regions exhibit normal amounts of interspecific divergence. Here we show that for 36 loci across the genomes of eight Lycopersicon species, naturally occurring DNA polymorphism (scaled by locus-specific divergence between species) is positively correlated with the density of crossing-over per physical length. Large between-species differences in the amount of DNA sequence polymorphism reflect breeding systems: selfing species show much less within-species polymorphism than outcrossing species. The strongest association of expected heterozygosity with crossing-over is found in species with intermediate levels of average nucleotide diversity. All of these observations appear to be in qualitative agreement with the hitchhiking effects caused by the fixation of advantageous mutations and/or “background selection” against deleterious mutations.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Soibam ◽  
Ayzhamal Zhamangaraeva

Abstract Background Chromosomes are organized into units called topologically associated domains (TADs). TADs dictate regulatory landscapes and other DNA-dependent processes. Even though various factors that contribute to the specification of TADs have been proposed, the mechanism is not fully understood. Understanding the process for specification and maintenance of these units is essential in dissecting cellular processes and disease mechanisms. Results In this study, we report a genome-wide study that considers the idea of long noncoding RNAs (lncRNAs) mediating chromatin organization using lncRNA:DNA triplex-forming sites (TFSs). By analyzing the TFSs of expressed lncRNAs in multiple cell lines, we find that they are enriched in TADs, their boundaries, and loop anchors. However, they are evenly distributed across different regions of a TAD showing no preference for any specific portions within TADs. No relationship is observed between the locations of these TFSs and CTCF binding sites. However, TFSs are located not just in promoter regions but also in intronic, intergenic, and 3’UTR regions. We also show these triplex-forming sites can be used as predictors in machine learning models to discriminate TADs from other genomic regions. Finally, we compile a list of important “TAD-lncRNAs” which are top predictors for TADs identification. Conclusions Our observations advocate the idea that lncRNA:DNA TFSs are positioned at specific areas of the genome organization and are important predictors for TADs. LncRNA:DNA triplex formation most likely is a general mechanism of action exhibited by some lncRNAs, not just for direct gene regulation but also to mediate 3D chromatin organization.


Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 247-258 ◽  
Author(s):  
Jinghong Li ◽  
Willis X Li

Abstract Overactivation of receptor tyrosine kinases (RTKs) has been linked to tumorigenesis. To understand how a hyperactivated RTK functions differently from wild-type RTK, we conducted a genome-wide systematic survey for genes that are required for signaling by a gain-of-function mutant Drosophila RTK Torso (Tor). We screened chromosomal deficiencies for suppression of a gain-of-function mutation tor (torGOF), which led to the identification of 26 genomic regions that, when in half dosage, suppressed the defects caused by torGOF. Testing of candidate genes in these regions revealed many genes known to be involved in Tor signaling (such as those encoding the Ras-MAPK cassette, adaptor and structural molecules of RTK signaling, and downstream target genes of Tor), confirming the specificity of this genetic screen. Importantly, this screen also identified components of the TGFβ (Dpp) and JAK/STAT pathways as being required for TorGOF signaling. Specifically, we found that reducing the dosage of thickveins (tkv), Mothers against dpp (Mad), or STAT92E (aka marelle), respectively, suppressed torGOF phenotypes. Furthermore, we demonstrate that in torGOF embryos, dpp is ectopically expressed and thus may contribute to the patterning defects. These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2573
Author(s):  
Yi-Hsiu Chung ◽  
Cheng-Kun Tsai ◽  
Ching-Fang Yu ◽  
Wan-Ling Wang ◽  
Chung-Lin Yang ◽  
...  

Purpose: By taking advantage of 18F-FDG PET imaging and tissue nuclear magnetic resonance (NMR) metabolomics, we examined the dynamic metabolic alterations induced by liver irradiation in a mouse model for hepatocellular carcinoma (HCC). Methods: After orthotopic implantation with the mouse liver cancer BNL cells in the right hepatic lobe, animals were divided into two experimental groups. The first received irradiation (RT) at 15 Gy, while the second (no-RT) did not. Intergroup comparisons over time were performed, in terms of 18F-FDG PET findings, NMR metabolomics results, and the expression of genes involved in inflammation and glucose metabolism. Results: As of day one post-irradiation, mice in the RT group showed an increased 18F-FDG uptake in the right liver parenchyma compared with the no-RT group. However, the difference reached statistical significance only on the third post-irradiation day. NMR metabolomics revealed that glucose concentrations peaked on day one post-irradiation both, in the right and left lobes—the latter reflecting a bystander effect. Increased pyruvate and glutamate levels were also evident in the right liver on the third post-irradiation day. The expression levels of the glucose-6-phosphatase (G6PC) and fructose-1, 6-bisphosphatase 1 (FBP1) genes were down-regulated on the first and third post-irradiation days, respectively. Therefore, liver irradiation was associated with a metabolic shift from an impaired gluconeogenesis to an enhanced glycolysis from the first to the third post-irradiation day. Conclusion: Radiation-induced metabolic alterations in the liver parenchyma occur as early as the first post-irradiation day and show dynamic changes over time.


2021 ◽  
Author(s):  
Nicolas Pompidor ◽  
Carine Charron ◽  
Catherine Hervouet ◽  
Stéphanie Bocs ◽  
Gaëtan Droc ◽  
...  

Abstract Background and Aims Modern sugarcane cultivars (Saccharum spp.) are high polyploids, aneuploids (2n = ~12x = ~120) derived from interspecific hybridizations between the domesticated sweet species Saccharum officinarum and the wild species S. spontaneum. Methods To analyse the architecture and origin of such a complex genome, we analysed the sequences of all 12 hom(oe)ologous haplotypes (BAC clones) from two distinct genomic regions of a typical modern cultivar, as well as the corresponding sequence in Miscanthus sinense and Sorghum bicolor, and monitored their distribution among representatives of the Saccharum genus. Key Results The diversity observed among haplotypes suggested the existence of three founding genomes (A, B, C) in modern cultivars, which diverged between 0.8 and 1.3 Mya. Two genomes (A, B) were contributed by S. officinarum; these were also found in its wild presumed ancestor S. robustum, and one genome (C) was contributed by S. spontaneum. These results suggest that S. officinarum and S. robustum are derived from interspecific hybridization between two unknown ancestors (A and B genomes). The A genome contributed most haplotypes (nine or ten) while the B and C genomes contributed one or two haplotypes in the regions analysed of this typical modern cultivar. Interspecific hybridizations likely involved accessions or gametes with distinct ploidy levels and/or were followed by a series of backcrosses with the A genome. The three founding genomes were found in all S. barberi, S. sinense and modern cultivars analysed. None of the analysed accessions contained only the A genome or the B genome, suggesting that representatives of these founding genomes remain to be discovered. Conclusions This evolutionary model, which combines interspecificity and high polyploidy, can explain the variable chromosome pairing affinity observed in Saccharum. It represents a major revision of the understanding of Saccharum diversity.


2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Martin Johnsson ◽  
Andrew Whalen ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Ching-Yi Chen ◽  
...  

Abstract Background Meiotic recombination results in the exchange of genetic material between homologous chromosomes. Recombination rate varies between different parts of the genome, between individuals, and is influenced by genetics. In this paper, we assessed the genetic variation in recombination rate along the genome and between individuals in the pig using multilocus iterative peeling on 150,000 individuals across nine genotyped pedigrees. We used these data to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig. Results Our results confirmed known features of the recombination landscape of the pig genome, including differences in genetic length of chromosomes and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, there were differences in average autosome-wide recombination rate between lines. The heritability of autosome-wide recombination rate was low but not zero (on average 0.07 for females and 0.05 for males). We found six genomic regions that are associated with recombination rate, among which five harbour known candidate genes involved in recombination: RNF212, SHOC1, SYCP2, MSH4 and HFM1. Conclusions Our results on the variation in recombination rate in the pig genome agree with those reported for other vertebrates, with a low but nonzero heritability, and the identification of a major quantitative trait locus for recombination rate that is homologous to that detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.


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