Genetics

  • Article
    | Open Access

    Little is known on how mitonuclear interactions influence genomic divergence among hybrid and parental lineages. A study of hybridizing wood warbler species complex finds a nuclear gene block with mitochondrial functions coevolves with mitochondrial genome, driven by climate-associated divergent selection underlying hybrid-parental population divergence.

    • Silu Wang
    • , Madelyn J. Ore
    •  & Darren Irwin
  • Article
    | Open Access

    The virulence of some infectious diseases seems to depend on the sex of the host the infection came from, as well as that of the current host. Here, McLeod et al. develop an epidemiological model to investigate the evolution of virulence when pathogens can retain epigenetic memories of their previous host.

    • David V. McLeod
    • , Geoff Wild
    •  & Francisco Úbeda
  • Article
    | Open Access

    Kras is frequently mutated in lung cancer and two isoforms are generated via alternative splicing. Here, the authors show that the two isoforms have divergent roles in cancer stem cells and the main tumour cell population, which are regulated by hypoxia and endoplasmic reticulum stress.

    • Wei-Ching Chen
    • , Minh D. To
    •  & Allan Balmain
  • Article
    | Open Access

    Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues and found 5hmC shows tissue-specific patterns.

    • Bo He
    • , Chao Zhang
    •  & Chengqi Yi
  • Article
    | Open Access

    Single-cell RNA-seq reveals the cellular heterogeneity in development and disease. Here the authors present a single-nucleus RNA-seq2 that allows deep characterization of nuclei isolated from frozen archived tissues, apply it for transcriptional profiling of individual hepatocytes, and determine a functional crosstalk between liver zonation and ploidy.

    • M. L. Richter
    • , I. K. Deligiannis
    •  & C. P. Martinez-Jimenez
  • Article
    | Open Access

    Welwitschia mirabilis is a unique plant that only has two leaves, but it can survive in hostile conditions of the African desert. Here, the authors report its chromosome-level genome assembly and discuss how gene function and regulation have given rise to its unique morphology and environmental adaptions.

    • Tao Wan
    • , Zhiming Liu
    •  & Qingfeng Wang
  • Article
    | Open Access

    Stable epigenetic changes are relatively rare. Here the authors report that mating induces stable silencing of a single-copy transgene in C. elegans. Components of small RNA silencing are required for this stable silencing.

    • Sindhuja Devanapally
    • , Pravrutha Raman
    •  & Antony M. Jose
  • Article
    | Open Access

    Mutations in 5’ untranslated regions (UTRs) have a functional role in gene expression in cancer. Here, the authors develop a sequencing-based high throughput functional assay named PLUMAGE and show the effects of these mutations on gene expression and their association with clinical outcomes in prostate cancer.

    • Yiting Lim
    • , Sonali Arora
    •  & Andrew C. Hsieh
  • Article
    | Open Access

    Existing genetic prediction tools typically assume that genetic variants contribute equally towards the phenotype. The authors develop eight prediction tools that allow the user to specify the heritability model, and show that these tools enable substantially improved prediction of complex traits.

    • Qianqian Zhang
    • , Florian Privé
    •  & Doug Speed
  • Article
    | Open Access

    Mosaic loss of chromosome Y (LOY) is a common form of clonal mosaicism in leukocytes. Here, the authors extend genetic association analyses to rare variation using exome-sequence data from 82,277 males, finding that loss-of-function alleles in GIGYF1 are associated with six-fold higher susceptibility to both LOY and Type 2 Diabetes.

    • Yajie Zhao
    • , Stasa Stankovic
    •  & John R. B. Perry
  • Article
    | Open Access

    While many genetic loci have been found to be associated with disease, not many have had their causal variants and mechanisms investigated. Here, the authors experimentally dissect two loci near GDF5 which are associated with two different joint disorders and which map to independent regulatory elements.

    • Pushpanathan Muthuirulan
    • , Dewei Zhao
    •  & Terence D. Capellini
  • Article
    | Open Access

    Pecan is an important specialty crop that has experienced extensive interspecific hybridization and nearly-obligate outcrossing. Here, the authors assemble diploid genomes of four outbred genotypes, identify interspecific introgressions through comparative genomics analyses, and map QTLs associated with pest resistance.

    • John T. Lovell
    • , Nolan B. Bentley
    •  & Jennifer J. Randall
  • Article
    | Open Access

    Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.

    • Chi Zhang
    • , Filippo Macchi
    •  & Kirsten C. Sadler
  • Article
    | Open Access

    α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

    • Franziska R. Traube
    • , Dilara Özdemir
    •  & Thomas Carell
  • Article
    | Open Access

    Ataxia Telangiectasia and Rad3-related (ATR) is a key regulator of replication stress response; yet, mutations within the ATR gene cause human ATR-Seckel Syndrome associated with microcephaly and intellectual disability. Here, the authors show neuron-specific ATR deletion increases intrinsic neuronal and epileptiform activity, revealing a function of ATR beyond its role in DNA damage response.

    • Murat Kirtay
    • , Josefine Sell
    •  & Zhao-Qi Wang
  • Article
    | Open Access

    How natural selection shapes the rate and molecular spectrum of mutations is debated. Yeast mutation accumulation experiments identify a gene promoting mutagenesis and show stabilizing selection maintaining the mutation rate above the drift barrier. Selection also preserves the mutation spectrum.

    • Haoxuan Liu
    •  & Jianzhi Zhang
  • Article
    | Open Access

    Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

    • Min-A Jhun
    • , Michael Mendelson
    •  & Themistocles L. Assimes
  • Article
    | Open Access

    The evolutionary and domestication history of apricots is poorly understood. Here, the authors provide four apricot high-quality genome assemblies, the genomes of 578 accessions from natural and cultivated populations, and show that Chinese and European apricots constitute two different gene pools, resulting from independent domestication events.

    • Alexis Groppi
    • , Shuo Liu
    •  & Véronique Decroocq
  • Article
    | Open Access

    The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

    • Benxia Hu
    • , Hyejung Won
    •  & Daniel H. Geschwind
  • Article
    | Open Access

    Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

    • Jun Lu
    • , Yongfeng Ding
    •  & Lisong Teng
  • Article
    | Open Access

    The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.

    • Lorena Buono
    • , Jorge Corbacho
    •  & Juan-Ramón Martínez-Morales
  • Article
    | Open Access

    The metaphor of an adaptive landscape is presented quantitatively by looking at molecular adaptations and their catalytic consequences in a recently evolved bacterial enzyme. The study identifies both genotype-by-environment interactions and environment-dependent epistasis as factors that can alter the fitness of functional mutations.

    • Dave W. Anderson
    • , Florian Baier
    •  & Nobuhiko Tokuriki
  • Article
    | Open Access

    Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

    • Yu-chi Shen
    • , Adrienne Niederriter Shami
    •  & Saher Sue Hammoud
  • Article
    | Open Access

    Although CTCF is a well-established 3D chromatin organizer in multicellular eukaryotes, relatively little is known about its male germ cell-specific paralogue, BORIS. Here the authors investigate how CTCF and BORIS interact and compensate in the male germline of mice to ensure appropriate activation of spermatogenesis-specific genes.

    • Samuel Rivero-Hinojosa
    • , Elena M. Pugacheva
    •  & Victor V. Lobanenkov
  • Article
    | Open Access

    Telomeres suppress the DNA damage response at chromosome ends. Here the authors show that in budding yeast the activity of the MRX complex in DNA repair and DNA damage signaling is inhibited by telomeric protein Rif2 via a short motif at the N-terminus.

    • Freddy Khayat
    • , Elda Cannavo
    •  & Alessandro Bianchi
  • Article
    | Open Access

    R loops are formed when single-stranded RNA anneals to one strand of DNA, forming three-stranded structures containing DNA-RNA hybrids and the displaced non-template single-stranded DNA. Here the authors reveal that the DNA:RNA helicase UPF1 plays a role in promoting R loops formation at telomeric double strand breaks to stimulate DNA resection and repair.

    • Greg H. P. Ngo
    • , Julia W. Grimstead
    •  & Duncan M. Baird
  • Article
    | Open Access

    In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.

    • Laura Santini
    • , Florian Halbritter
    •  & Martin Leeb
  • Article
    | Open Access

    Resistance of Neisseria gonorrhoeae to extended spectrum cephalosporins is an increasing concern. Here, the authors conduct whole genome sequencing of isolates from the United States and find that most resistant isolates were associated with a persistent circulating lineage.

    • Jesse C. Thomas IV
    • , Sandeep J. Joseph
    •  & Zach Perry
  • Article
    | Open Access

    The extracellular Contractile Injection System (eCIS) is a toxin-delivery particle that mediates interactions between bacteria and their invertebrate hosts. Here, the authors catalogue eCIS loci from 1,249 prokaryotic genomes, showing enrichment in non-pathogenic environmental microbes, and identifying eCIS-associated toxins that inhibit the growth of bacteria and/or yeast.

    • Alexander Martin Geller
    • , Inbal Pollin
    •  & Asaf Levy
  • Article
    | Open Access

    The E3 ligase Hakai can interact with the m6A methylation machinery but its function is still unclear. Here, the authors show that Hakai is a conserved component of the m6A methyltransferase complex and provide functional and molecular insights into its role in regulating m6A levels in Drosophila.

    • Praveen Bawankar
    • , Tina Lence
    •  & Jean-Yves Roignant
  • Article
    | Open Access

    Cortical excitatory/inhibitory (E/I) imbalance is a feature of autism spectrum disorder (ASD). Here, the authors show that FoxG1 regulates the formation of cortical GABAergic circuits affecting social behaviour during a specific postnatal time window in mouse models of ASD.

    • Goichi Miyoshi
    • , Yoshifumi Ueta
    •  & Mariko Miyata
  • Article
    | Open Access

    Pernicious anemia shows co-incidence with autoimmune disorders, yet the genetic basis for this condition is understudied. Here, the authors perform a genome-wide association study meta-analysis on pernicious anemia, identifying five susceptibility loci that map to genes with known roles in autoimmune disease.

    • Triin Laisk
    • , Maarja Lepamets
    •  & Reedik Mägi
  • Article
    | Open Access

    The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m6A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m6A methylation activity of the complex.

    • Xiaona Liu
    • , Hailong Wang
    •  & Shan Xiao
  • Article
    | Open Access

    A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

    • Long Jin
    • , Qianzi Tang
    •  & Mingzhou Li