Inference of selective forces on house mouse genomes during secondary contact in East Asia [RESEARCH]
The house mouse (Mus musculus), which is commensal to humans, has spread globally via human activities, leading to secondary contact between genetically divergent subspecies. This pattern of genetic admixture can provide insights into the selective forces at play in this well-studied model organism. Our analysis of 163 house mouse genomes, with a particular focus on East Asia, revealed substantial admixture between the subspecies castaneus and musculus, particularly in Japan and southern China. We revealed, despite the different level of autosomal admixture among regions, that all Y Chromosomes in the East Asian samples be...
Source: Genome Research - April 18, 2024 Category: Genetics & Stem Cells Authors: Fujiwara, K., Kubo, S., Endo, T., Takada, T., Shiroishi, T., Suzuki, H., Osada, N. Tags: RESEARCH Source Type: research
Probabilistic association of differentially expressed genes with cis-regulatory elements [METHOD]
Differential gene expression in response to perturbations is mediated at least in part by changes in binding of transcription factors (TFs) and other proteins at specific genomic regions. Association of these cis-regulatory elements (CREs) with their target genes is a challenging task that is essential to address many biological and mechanistic questions. Many current approaches rely on chromatin conformation capture techniques or single-cell correlational methods to establish CRE-to-gene associations. These methods can be effective but have limitations, including resolution, gaps in detectable association distances, and c...
Source: Genome Research - April 17, 2024 Category: Genetics & Stem Cells Authors: Roberts, B. S., Anderson, A. G., Partridge, C., Cooper, G. M., Myers, R. M. Tags: METHOD Source Type: research
A systematic review on the biochemical threshold of mitochondrial genetic variants [REVIEW]
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measu...
Source: Genome Research - April 16, 2024 Category: Genetics & Stem Cells Authors: Smith, K. K., Moreira, J. D., Wilson, C. R., Padera, J. O., Lamason, A. N., Xue, L., Gopal, D. M., Flynn, D. B., Fetterman, J. L. Tags: REVIEW Source Type: research
Phased nanopore assembly with Shasta and modular graph phasing with GFAse [METHOD]
Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of ONT Prome...
Source: Genome Research - April 16, 2024 Category: Genetics & Stem Cells Authors: Lorig-Roach, R., Meredith, M., Monlong, J., Jain, M., Olsen, H., McNulty, B., Porubsky, D., Montague, T., Lucas, J., Condon, C., Eizenga, J. M., Juul, S., McKenzie, S., Simmonds, S. E., Park, J., Asri, M., Koren, S., Eichler, E., Axel, R., Martin, B., Car Tags: METHOD Source Type: research
Robust chromatin state annotation [METHOD]
With the goal of mapping genomic activity, international projects have recently measured epigenetic activity in hundreds of cell and tissue types. Chromatin state annotations produced by segmentation and genome annotation (SAGA) methods have emerged as the predominant way to summarize these epigenomic data sets in order to annotate the genome. These chromatin state annotations are essential for many genomic tasks, including identifying active regulatory elements and interpreting disease-associated genetic variation. However, despite the widespread applications of SAGA methods, no principled approach exists to evaluate the ...
Source: Genome Research - April 16, 2024 Category: Genetics & Stem Cells Authors: Foroozandeh Shahraki, M., Farahbod, M., Libbrecht, M. W. Tags: METHOD Source Type: research
Extreme genome scrambling in marine planktonic Oikopleura dioica cryptic species [RESEARCH]
Genome structural variations within species are rare. How selective constraints preserve gene order and chromosome structure is a central question in evolutionary biology that remains unsolved. Our sequencing of several genomes of the appendicularian tunicate Oikopleura dioica around the globe reveals extreme genome scrambling caused by thousands of chromosomal rearrangements, although showing no obvious morphological differences between these animals. The breakpoint accumulation rate is an order of magnitude higher than in ascidian tunicates, nematodes, Drosophila, or mammals. Chromosome arms and sex-specific regions appe...
Source: Genome Research - April 15, 2024 Category: Genetics & Stem Cells Authors: Plessy, C., Mansfield, M. J., Bliznina, A., Masunaga, A., West, C., Tan, Y., Liu, A. W., Grasic, J., del Rio Pisula, M. S., Sanchez-Serna, G., Fabrega-Torrus, M., Ferrandez-Roldan, A., Roncalli, V., Navratilova, P., Thompson, E. M., Onuma, T., Nishida, H. Tags: RESEARCH Source Type: research
The genome of the colonial hydroid Hydractinia reveals that their stem cells use a toolkit of evolutionarily shared genes with all animals [RESOURCES]
Hydractinia is a colonial marine hydroid that shows remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, Hydractinia symbiolongicarpus and Hydractinia echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell-type marker...
Source: Genome Research - April 15, 2024 Category: Genetics & Stem Cells Authors: Schnitzler, C. E., Chang, E. S., Waletich, J., Quiroga-Artigas, G., Wong, W. Y., Nguyen, A.-D., Barreira, S. N., Doonan, L. B., Gonzalez, P., Koren, S., Gahan, J. M., Sanders, S. M., Bradshaw, B., DuBuc, T. Q., Febrimarsa, , de Jong, D., Nawrocki, E. P., Tags: RESOURCES Source Type: research
Systematic identification and characterization of exon-intron circRNAs [RESEARCH]
Exon–intron circRNAs (EIciRNAs) are a circRNA subclass with retained introns. Global features of EIciRNAs remain largely unexplored, mainly owing to the lack of bioinformatic tools. The regulation of intron retention (IR) in EIciRNAs and the associated functionality also require further investigation. We developed a framework, FEICP, which efficiently detected EIciRNAs from high-throughput sequencing (HTS) data. EIciRNAs are distinct from exonic circRNAs (EcircRNAs) in aspects such as with larger length, localization in the nucleus, high tissue specificity, and enrichment mostly in the brain. Deep learning analyses r...
Source: Genome Research - April 12, 2024 Category: Genetics & Stem Cells Authors: Zhong, Y., Yang, Y., Wang, X., Ren, B., Wang, X., Shan, G., Chen, L. Tags: RESEARCH Source Type: research
Experimentally evolving Drosophila erecta populations may fail to establish an effective piRNA-based host defense against invading P-elements [RESEARCH]
To prevent the spread of transposable elements (TEs), hosts have developed sophisticated defense mechanisms. In mammals and invertebrates, a major defense mechanism operates through PIWI-interacting RNAs (piRNAs). To investigate the establishment of the host defense, we introduced the P-element, one of the most widely studied eukaryotic transposons, into naive lines of Drosophila erecta. We monitored the invasion in three replicates for more than 50 generations by sequencing the genomic DNA (using short and long reads), the small RNAs, and the transcriptome at regular intervals. A piRNA-based host defense was rapidly estab...
Source: Genome Research - April 12, 2024 Category: Genetics & Stem Cells Authors: Selvaraju, D., Wierzbicki, F., Kofler, R. Tags: RESEARCH Source Type: research
Translation-dependent and -independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T cell activation [RESEARCH]
mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality-control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions, and the recruitment of specific proteins to ribosomes is an important determinant of mRNA turnover. However, the extent to which translation-dependent mRNA decay (TDD) and translation-independent mRNA decay (TID) pathways participate in the degradation of mRNAs has not been studied yet. Here we describe a comprehensive analysis of basal and signal-induced TDD and TID in mouse primary CD4+ T...
Source: Genome Research - April 11, 2024 Category: Genetics & Stem Cells Authors: Mercier, B. C., Labaronne, E., Cluet, D., Guiguettaz, L., Fontrodona, N., Bicknell, A., Corbin, A., Wencker, M., Aube, F., Modolo, L., Jouravleva, K., Auboeuf, D., Moore, M. J., Ricci, E. P. Tags: RESEARCH Source Type: research
Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites [RESEARCH]
Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause neglected tropical diseases, are a relevant group to study aneuploidies. Their life cycle has several stressors that could select for different patterns of chromosomal duplications and/or losses, and their nearly universal use o...
Source: Genome Research - April 11, 2024 Category: Genetics & Stem Cells Authors: Reis-Cunha, J. L., Pimenta-Carvalho, S. A., Almeida, L. V., Coqueiro-dos-Santos, A., Marques, C. A., Black, J. A., Damasceno, J., McCulloch, R., Bartholomeu, D. C., Jeffares, D. C. Tags: RESEARCH Source Type: research
Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model [RESEARCH]
Missense mutations in the gene encoding the microtubule-associated protein tau cause autosomal dominant forms of frontotemporal dementia. Multiple models of frontotemporal dementia based on transgenic expression of human tau in experimental model organisms, including Drosophila, have been described. These models replicate key features of the human disease, but do not faithfully recreate the genetic context of the human disorder. Here we use CRISPR-Cas mediated gene editing to model frontotemporal dementia caused by the tau P301L mutation by creating the orthologous mutation, P251L, in the endogenous Drosophila tau gene. Fl...
Source: Genome Research - April 10, 2024 Category: Genetics & Stem Cells Authors: Bukhari, H., Nithianadam, V., Battaglia, R. A., Cicalo, A., Sarkar, S., Comjean, A., Hu, Y., Leventhal, M. J., Dong, X., Feany, M. B. Tags: RESEARCH Source Type: research
Plant genome evolution in the genus Eucalyptus driven by structural rearrangements that promote sequence divergence [RESEARCH]
Genomes have a highly organized architecture (nonrandom organization of functional and nonfunctional genetic elements within chromosomes) that is essential for many biological functions, particularly, gene expression and reproduction. Despite the need to conserve genome architecture, a high level of structural variation has been observed within species. As species separate and diverge, genome architecture also diverges, becoming increasingly poorly conserved as divergence time increases. However, within plant genomes, the processes of genome architecture divergence are not well described. Here we use long-read sequencing a...
Source: Genome Research - April 8, 2024 Category: Genetics & Stem Cells Authors: Ferguson, S., Jones, A., Murray, K., Andrew, R., Schwessinger, B., Borevitz, J. O. Tags: RESEARCH Source Type: research
Accelerated somatic mutation calling for whole-genome and whole-exome sequencing data from heterogenous tumor samples [METHOD]
Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenge was overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multi-step parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE 2 speeds up 50 times than MuSE 1 and 8-80 times than other popular callers. Our benchmark study suggests combining MuSE 2 and the recently accelerated Strelka2 achieves high effi...
Source: Genome Research - April 8, 2024 Category: Genetics & Stem Cells Authors: Ji, S., Wang, W., Zhu, T., Sethia, A. Tags: METHOD Source Type: research
Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches [METHOD]
Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse...
Source: Genome Research - April 5, 2024 Category: Genetics & Stem Cells Authors: Lee, M., Guo, Q., Kim, M., Choi, J., Segura, A., Genceroglu, A., LeBlanc, L., Ramirez, N., Jang, Y. J., Jang, Y., Lee, B.-K., Marcotte, E. M., Kim, J. Tags: METHOD Source Type: research
