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Sunday, September 22, 2019

Epigenetic landscape influences the liver cancer genome architecture.

The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV)…

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Sunday, September 22, 2019

Double insertion of transposable elements provides a substrate for the evolution of satellite DNA.

Eukaryotic genomes are replete with repeated sequences in the form of transposable elements (TEs) dispersed across the genome or as satellite arrays, large stretches of tandemly repeated sequences. Many satellites clearly originated as TEs, but it is unclear how mobile genetic parasites can transform into megabase-sized tandem arrays. Comprehensive population genomic sampling is needed to determine the frequency and generative mechanisms of tandem TEs, at all stages from their initial formation to their subsequent expansion and maintenance as satellites. The best available population resources, short-read DNA sequences, are often considered to be of limited utility for analyzing repetitive DNA due…

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Sunday, September 22, 2019

The hpRNA/RNAi pathway is essential to resolve intragenomic conflict in the Drosophila male germline.

Intragenomic conflicts are fueled by rapidly evolving selfish genetic elements, which induce selective pressures to innovate opposing repressive mechanisms. This is patently manifest in sex-ratio (SR) meiotic drive systems, in which distorter and suppressor factors bias and restore equal transmission of X and Y sperm. Here, we reveal that multiple SR suppressors in Drosophila simulans (Nmy and Tmy) encode related hairpin RNAs (hpRNAs), which generate endo-siRNAs that repress the paralogous distorters Dox and MDox. All components in this drive network are recently evolved and largely testis restricted. To connect SR hpRNA function to the RNAi pathway, we generated D. simulans null…

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Sunday, September 22, 2019

Asymmetric processing of DNA ends at a double-strand break leads to unconstrained dynamics and ectopic translocation.

Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress potentially dangerous ectopic recombination. Both sequence and chromatin context are thought to influence pathway choice between non-homologous end-joining (NHEJ) and homology-driven recombination. To test the effect of repetitive sequences on break processing, we have inserted TG-rich repeats on one side of an inducible DSB at the budding yeast MAT locus on chromosome III. Five clustered Rap1 sites within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2 recruitment, impair resection, and favor elongation by telomerase. The two sides of the break lose end-to-end tethering and show enhanced, uncoordinated movement.…

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Sunday, September 22, 2019

Extraordinary genome instability and widespread chromosome rearrangements during vegetative growth

The haploid genome of the pathogenic fungus Zymoseptoria tritici is contained on “core” and “accessory” chromosomes. While 13 core chromosomes are found in all strains, as many as eight accessory chromosomes show presence/absence variation and rearrangements among field isolates. The factors influencing these presence/absence polymorphisms are so far unknown. We investigated chromosome stability using experimental evolution, karyotyping, and genome sequencing. We report extremely high and variable rates of accessory chromosome loss during mitotic propagation in vitro and in planta Spontaneous chromosome loss was observed in 2 to >50% of cells during 4 weeks of incubation. Similar rates of chromosome loss…

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Sunday, September 22, 2019

The genome of tapeworm Taenia multiceps sheds light on understanding parasitic mechanism and control of coenurosis disease.

Coenurosis, caused by the larval coenurus of the tapeworm Taenia multiceps, is a fatal central nervous system disease in both sheep and humans. Though treatment and prevention options are available, the control of coenurosis still faces presents great challenges. Here, we present a high-quality genome sequence of T. multiceps in which 240 Mb (96%) of the genome has been successfully assembled using Pacbio single-molecule real-time (SMRT) and Hi-C data with a N50 length of 44.8 Mb. In total, 49.5 Mb (20.6%) repeat sequences and 13, 013 gene models were identified. We found that Taenia spp. have an expansion of transposable…

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Sunday, September 22, 2019

Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.

Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedia. Using long-read sequencing, we generated the first complete and well-annotated genome assemblies of large, highly diverged, non-recombining regions associated with meiotic drive elements. Phylogenetic analysis shows that, even though Sk-2 and Sk-3 are located in the same chromosomal region, they do not form sister clades, suggesting independent origins or at least a long…

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Sunday, September 22, 2019

Genomic structural variations within five continental populations of Drosophila melanogaster.

Chromosomal structural variations (SV) including insertions, deletions, inversions, and translocations occur within the genome and can have a significant effect on organismal phenotype. Some of these effects are caused by structural variations containing genes. Large structural variations represent a significant amount of the genetic diversity within a population. We used a global sampling of Drosophila melanogaster (Ithaca, Zimbabwe, Beijing, Tasmania, and Netherlands) to represent diverse populations within the species. We used long-read sequencing and optical mapping technologies to identify SVs in these genomes. Among the five lines examined, we found an average of 2,928 structural variants within these genomes. These…

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Sunday, September 22, 2019

Constant conflict between Gypsy LTR retrotransposons and CHH methylation within a stress-adapted mangrove genome.

The evolutionary dynamics of the conflict between transposable elements (TEs) and their host genome remain elusive. This conflict will be intense in stress-adapted plants as stress can often reactivate TEs. Mangroves reduce TE load convergently in their adaptation to intertidal environments and thus provide a unique opportunity to address the host-TE conflict and its interaction with stress adaptation. Using the mangrove Rhizophora apiculata as a model, we investigated methylation and short interfering RNA (siRNA) targeting patterns in relation to the abundance and age of long terminal repeat (LTR) retrotransposons. We also examined the distance of LTR retrotransposons to genes, the…

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Sunday, September 22, 2019

Reassessment of the evolution of wheat chromosomes 4A, 5A, and 7B.

Comparison of genome sequences of wild emmer wheat and Aegilops tauschii suggests a novel scenario of the evolution of rearranged wheat chromosomes 4A, 5A, and 7B. Past research suggested that wheat chromosome 4A was subjected to a reciprocal translocation T(4AL;5AL)1 that occurred in the diploid progenitor of the wheat A subgenome and to three major rearrangements that occurred in polyploid wheat: pericentric inversion Inv(4AS;4AL)1, paracentric inversion Inv(4AL;4AL)1, and reciprocal translocation T(4AL;7BS)1. Gene collinearity along the pseudomolecules of tetraploid wild emmer wheat (Triticum turgidum ssp. dicoccoides, subgenomes AABB) and diploid Aegilops tauschii (genomes DD) was employed to confirm these rearrangements and…

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Sunday, September 22, 2019

Unexpected patterns of segregation distortion at a selfish supergene in the fire ant Solenopsis invicta.

The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this supergene – including suppressed recombination, presence of deleterious mutations, association with a large centromere, and “green-beard” behavior – suggest that it may be a selfish genetic element that engages in transmission ratio distortion (TRD), defined as significant departures in progeny allele frequencies from Mendelian inheritance ratios. We tested this possibility by surveying segregation ratios in embryo progenies of 101 queens…

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Sunday, September 22, 2019

Noise-Cancelling Repeat Finder: Uncovering tandem repeats in error-prone long-read sequencing data

Tandem DNA repeats can be sequenced with long-read technologies, but cannot be accurately deciphered due to the lack of computational tools taking high error rates of these technologies into account. Here we introduce Noise-Cancelling Repeat Finder (NCRF) to uncover putative tandem repeats of specified motifs in noisy long reads produced by Pacific Biosciences and Oxford Nanopore sequencers. Using simulations, we validated the use of NCRF to locate tandem repeats with motifs of various lengths and demonstrated its superior performance as compared to two alternative tools. Using real human whole-genome sequencing data, NCRF identified long arrays of the (AATGG)n repeat involved…

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Sunday, September 22, 2019

Loss of Rap1 supports recombination-based telomere maintenance independent of RNA-DNA hybrids in fission yeast

To investigate the molecular changes needed for cells to maintain their telomeres by recombination, we monitored telomere appearance during serial culture of fission yeast cells lacking the telomerase recruitment factor Ccq1. Rad52 is loaded onto critically short telomeres shortly after germination despite continued telomere erosion, suggesting that recruitment of recombination factors is not sufficient to maintain telomeres in the absence of telomerase function. Instead, survivor formation coincides with the derepression of telomeric repeat-containing RNA (TERRA). Degradation of telomere-associated TERRA in this context drives a severe growth crisis, ultimately leading to a distinct type of linear survivor with altered cytological telomere…

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Sunday, September 22, 2019

Meiotic drive of female-inherited supernumerary chromosomes in a pathogenic fungus.

Meiosis is a key cellular process of sexual reproduction that includes pairing of homologous sequences. In many species however, meiosis can also involve the segregation of supernumerary chromosomes, which can lack a homolog. How these unpaired chromosomes undergo meiosis is largely unknown. In this study we investigated chromosome segregation during meiosis in the haploid fungus Zymoseptoria tritici that possesses a large complement of supernumerary chromosomes. We used isogenic whole chromosome deletion strains to compare meiotic transmission of chromosomes when paired and unpaired. Unpaired chromosomes inherited from the male parent as well as paired supernumerary chromosomes in general showed Mendelian inheritance.…

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Sunday, September 22, 2019

Whole-genome landscape of Medicago truncatula symbiotic genes.

Advances in deciphering the functional architecture of eukaryotic genomes have been facilitated by recent breakthroughs in sequencing technologies, enabling a more comprehensive representation of genes and repeat elements in genome sequence assemblies, as well as more sensitive and tissue-specific analyses of gene expression. Here we show that PacBio sequencing has led to a substantially improved genome assembly of Medicago truncatula A17, a legume model species notable for endosymbiosis studies1, and has enabled the identification of genome rearrangements between genotypes at a near-base-pair resolution. Annotation of the new M. truncatula genome sequence has allowed for a thorough analysis of transposable elements…

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