Telomerase-independent survival leads to a mosaic of complex subtelomere rearrangements in Chlamydomonas reinhardtii [RESEARCH]
Telomeres and subtelomeres, the genomic regions located at chromosome extremities, are essential for genome stability in eukaryotes. In the absence of the canonical maintenance mechanism provided by telomerase, telomere shortening induces genome instability. The landscape of the ensuing genome rearrangements is not accessible by short-read sequencing. Here, we leverage Oxford Nanopore Technologies long-read sequencing to survey the extensive repertoire of genome rearrangements in telomerase mutants of the model green microalga Chlamydomonas reinhardtii. In telomerase-mutant strains grown for hundreds of generations, most c...
Source: Genome Research - October 4, 2023 Category: Genetics & Stem Cells Authors: Chaux, F., Agier, N., Garrido, C., Fischer, G., Eberhard, S., Xu, Z. Tags: RESEARCH Source Type: research
Genetic inhibitors of APOBEC3B-induced mutagenesis [RESEARCH]
The cytidine deaminases APOBEC3A (A3A) and APOBEC3B (A3B) are prominent mutators of human cancer genomes. However, tumor-specific genetic modulators of APOBEC-induced mutagenesis are poorly defined. Here, we used a screen to identify 61 gene deletions that increase A3B-induced mutations in yeast. We also determined whether each deletion was epistatic with Ung1 loss, which indicated whether the encoded factors participate in the homologous recombination (HR)–dependent bypass of A3B/Ung1-dependent abasic sites or suppress A3B-catalyzed deamination by protecting against aberrant formation of single-stranded DNA (ssDNA)....
Source: Genome Research - October 3, 2023 Category: Genetics & Stem Cells Authors: Mertz, T. M., Rice-Reynolds, E., Nguyen, L., Wood, A., Cordero, C., Bray, N., Harcy, V., Vyas, R. K., Mitchell, D., Lobachev, K., Roberts, S. A. Tags: RESEARCH Source Type: research
The predicted RNA-binding protein regulome of axonal mRNAs [RESEARCH]
Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their cytoarchitecture. The targeting of RNA transcripts to axons is one of the mechanisms that allows rapid local translation of proteins in response to extracellular signals. 3' Untranslated regions (UTRs) of mRNA are noncoding sequences that play a critical role in determining transcript localization and translation by interacting with specific RNA-binding proteins (RBPs). However, how 3' UTRs contribute to mRNA metabolism and the nature of RBP complexes responsible for these functions remains el...
Source: Genome Research - October 3, 2023 Category: Genetics & Stem Cells Authors: Luisier, R., Andreassi, C., Fournier, L., Riccio, A. Tags: RESEARCH Source Type: research
Spatial transcriptomics reveals asymmetric cellular responses to injury in the regenerating spiny mouse (Acomys) ear [RESOURCES]
In contrast to other mammals, the spiny mouse (Acomys) regenerates skin and ear tissue, which includes hair follicles, glands, and cartilage, in a scar-free manner. Ear punch regeneration is asymmetric with only the proximal wound side participating in regeneration. Here, we show that cues originating from the proximal side are required for normal regeneration and use spatially resolved transcriptomics (tomo-seq) to understand the molecular and cellular events underlying this process. Analyzing gene expression across the ear and comparing expression modules between proximal and distal wound sides, we identify asymmetric ge...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: van Beijnum, H., Koopmans, T., Tomasso, A., Disela, V., te Lindert, S., Bakkers, J., Alemany, A., Berezikov, E., Bartscherer, K. Tags: RESOURCES Source Type: research
Genetic features and genomic targets of human KRAB-zinc finger proteins [RESOURCES]
Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KZFPs) are one of the largest groups of transcription factors encoded by tetrapods, with 378 members in human alone. KZFP genes are often grouped in clusters reflecting amplification by gene and segment duplication since the gene family first emerged more than 400 million years ago. Previous work has revealed that many KZFPs recognize transposable element (TE)-embedded sequences as genomic targets, and that KZFPs facilitate the co-option of the regulatory potential of TEs for the benefit of the host. Here, we present a comprehensive survey of the...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: de Tribolet-Hardy, J., Thorball, C. W., Forey, R., Planet, E., Duc, J., Coudray, A., Khubieh, B., Offner, S., Pulver, C., Fellay, J., Imbeault, M., Turelli, P., Trono, D. Tags: RESOURCES Source Type: research
Unraveling the palindromic and nonpalindromic motifs of retroviral integration site sequences by statistical mixture models [METHODS]
A weak palindromic nucleotide motif is the hallmark of retroviral integration site alignments. Given that the majority of target sequences are not palindromic, the current model explains the symmetry by an overlap of the nonpalindromic motif present on one of the half-sites of the sequences. Here, we show that the implementation of multicomponent mixture models allows for different interpretations consistent with the existence of both palindromic and nonpalindromic submotifs in the sets of integration site sequences. We further show that the weak palindromic motifs result from freely combined site-specific submotifs restri...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Miklik, D., Grim, J., Elleder, D., Hejnar, J. Tags: METHODS Source Type: research
A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures [METHODS]
Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the "Mouse Aging Cell Atlas" (Tabula Muris Senis) data, we identified tissue-level transcriptomic aging programs for more than 20 murine tissues and create...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Mao, S., Su, J., Wang, L., Bo, X., Li, C., Chen, H. Tags: METHODS Source Type: research
Allele-specific RNA N6-methyladenosine modifications reveal functional genetic variants in human tissues [METHODS]
An intricate network of cis- and trans-elements acts on RNA N6-methyladenosine (m6A), which in turn may affect gene expression and, ultimately, human health. A complete understanding of this network requires new approaches to accurately measure the subtle m6A differences arising from genetic variants, many of which have been associated with common diseases. To address this gap, we developed a method to accurately and sensitively detect transcriptome-wide allele-specific m6A (ASm6A) from MeRIP-seq data and applied it to uncover 12,056 high-confidence ASm6A modifications from 25 human tissues. We also identified 1184 putativ...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Cao, S., Zhu, H., Cui, J., Liu, S., Li, Y., Shi, J., Mo, J., Wang, Z., Wang, H., Hu, J., Chen, L., Li, Y., Xia, L., Xiao, S. Tags: METHODS Source Type: research
Diffusion-enhanced characterization of 3D chromatin structure reveals its linkage to gene regulatory networks and the interactome [METHODS]
The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CTG), to obtain reliable geometric information on the chromatin from Hi-C data. CTG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions. The genomic structure yielded by CTG serves as an architectural...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: He, Y., Xue, Y., Wang, J., Huang, Y., Liu, L., Huang, Y., Gao, Y. Q. Tags: METHODS Source Type: research
Copy number variation alters local and global mutational tolerance [RESEARCH]
Copy number variants (CNVs), duplications and deletions of genomic sequences, contribute to evolutionary adaptation but can also confer deleterious effects and cause disease. Whereas the effects of amplifying individual genes or whole chromosomes (i.e., aneuploidy) have been studied extensively, much less is known about the genetic and functional effects of CNVs of differing sizes and structures. Here, we investigated Saccharomyces cerevisiae (yeast) strains that acquired adaptive CNVs of variable structures and copy numbers following experimental evolution in glutamine-limited chemostats. Although beneficial in the select...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Avecilla, G., Spealman, P., Matthews, J., Caudal, E., Schacherer, J., Gresham, D. Tags: RESEARCH Source Type: research
Transposable elements drive the evolution of metazoan zinc finger genes [RESEARCH]
Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid expansion and contraction of numerous subfamilies across the animal phylogeny. The forces and mechanisms underlying rapid ZNF evolution remain poorly understood, but there is growing evidence that, in tetrapods, the targeting and repression of lineage-specific transposable elements (TEs) plays a critical role in the evolution of the Krüppel-associated box ZNF (KZNF) subfamily. Currently, it is unknown whether this function and coevolutionary relationship is...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Wells, J. N., Chang, N.-C., McCormick, J., Coleman, C., Ramos, N., Jin, B., Feschotte, C. Tags: RESEARCH Source Type: research
Extensive variation in germline de novo mutations in Poecilia reticulata [RESEARCH]
The rate of germline mutation is fundamental to evolutionary processes, as it generates the variation upon which selection acts. The guppy, Poecilia reticulata, is a model of rapid adaptation, however the relative contribution of standing genetic variation versus de novo mutation (DNM) to evolution in this species remains unclear. Here, we use pedigree-based approaches to quantify and characterize germline DNMs in three large guppy families. Our results suggest germline mutation rate in the guppy varies substantially across individuals and families. Most DNMs are shared across multiple siblings, suggesting they arose durin...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Lin, Y., Darolti, I., van der Bijl, W., Morris, J., Mank, J. E. Tags: RESEARCH Source Type: research
Historical RNA expression profiles from the extinct Tasmanian tiger [RESEARCH]
Paleogenomics continues to yield valuable insights into the evolution, population dynamics, and ecology of our ancestors and other extinct species. However, DNA sequencing cannot reveal tissue-specific gene expression, cellular identity, or gene regulation, which are only attainable at the transcriptional level. Pioneering studies have shown that useful RNA can be extracted from ancient specimens preserved in permafrost and historical skins from extant canids, but no attempts have been made so far on extinct species. We extract, sequence, and analyze historical RNA from muscle and skin tissue of a ~130-year-old Tasmanian t...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Marmol-Sanchez, E., Fromm, B., Oskolkov, N., Pochon, Z., Kalogeropoulos, P., Eriksson, E., Biryukova, I., Sekar, V., Ersmark, E., Andersson, B., Dalen, L., Friedländer, M. R. Tags: RESEARCH Source Type: research
A Chinese indicine pangenome reveals a wealth of novel structural variants introgressed from other Bos species [RESEARCH]
Chinese indicine cattle harbor a much higher genetic diversity compared with other domestic cattle, but their genome architecture remains uninvestigated. Using PacBio HiFi sequencing data from 10 Chinese indicine cattle across southern China, we assembled 20 high-quality partially phased genomes and integrated them into a multiassembly graph containing 148.5 Mb (5.6%) of novel sequence. We identified 156,009 high-confidence nonredundant structural variants (SVs) and 206 SV hotspots spanning ~195 Mb of gene-rich sequence. We detected 34,249 archaic introgressed fragments in Chinese indicine cattle covering 1.93 Gb (73.3%) o...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Dai, X., Bian, P., Hu, D., Luo, F., Huang, Y., Jiao, S., Wang, X., Gong, M., Li, R., Cai, Y., Wen, J., Yang, Q., Deng, W., Nanaei, H. A., Wang, Y., Wang, F., Zhang, Z., Rosen, B. D., Heller, R., Jiang, Y. Tags: RESEARCH Source Type: research
Ultra-long-range interactions between active regulatory elements [RESEARCH]
Contacts between enhancers and promoters are thought to relate to their ability to activate transcription. Investigating factors that contribute to such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies between millions of pairs of cis-regulatory elements from chromosome conformation capture data sets and analyzed a collection of hundreds of DNA-binding factors for binding at regions of enriched contacts. This analysis revealed enriched contacts at sites bound by many factors associated with active transcription. We show that active regulatory elem...
Source: Genome Research - September 28, 2023 Category: Genetics & Stem Cells Authors: Friman, E. T., Flyamer, I. M., Marenduzzo, D., Boyle, S., Bickmore, W. A. Tags: RESEARCH Source Type: research
