The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can

Plant intra-individual and inter-individual variation can be determined by the epigenome, a set of covalent modifications of DNA and chromatin that can alter genome structure and activity without changes to the genome sequence. The epigenome of plant cells is plastic, that is, it can change in response to internal or external cues, such as during development or due to environmental changes, to create

Three recent studies report the generation of miniature CRISPR systems based on compact Cas effector proteins, showing high efficiency of genome editing or transcriptional regulation in mammalian cells.

Four new studies in Nature report multi-tissue analyses of somatic mutations from human donors, with insights into cell lineage commitment during embryonic development, as well as tissue-specific aspects of mutagenesis.

Human physiology is likely to have been selected for endurance physical activity. However, modern humans have become largely sedentary, with physical activity becoming a leisure-time pursuit for most. Whereas inactivity is a strong risk factor for disease, regular physical activity reduces the risk of chronic disease and mortality. Although substantial epidemiological evidence supports the beneficial

This molecular phenotyping study shows that common variants in mitochondrial DNA associated with diseases of ageing influence cellular protein homeostasis, and that this link is mediated by circulating levels of N-formylmethionine, the initiating amino acid in mitochondrial protein synthesis.

Many enhancers exist as clusters in the genome, which has led to the coining of the term ‘super-enhancer’. In this Viewpoint, five experts discuss our biological understanding of enhancer clusters, how we can responsibly study their functions, and their opinions on whether names for enhancer clusters are an informative reflection of their functional properties. They also provide their thoughts on key

A new study in Nature reports a large-scale genome-wide association study of menopause timing, revealing mechanistic details and potential therapeutic opportunities for preserving human fertility.

The rapidly emerging field of macrogenetics focuses on analysing publicly accessible genetic datasets from thousands of species to explore large-scale patterns and predictors of intraspecific genetic variation. Facilitated by advances in evolutionary biology, technology, data infrastructure, statistics and open science, macrogenetics addresses core evolutionary hypotheses (such as disentangling environmental

Animal hosts have initiated myriad symbiotic associations with microorganisms and often have maintained these symbioses for millions of years, spanning drastic changes in ecological conditions and lifestyles. The establishment and persistence of these relationships require genetic innovations on the parts of both symbionts and hosts. The nature of symbiont innovations depends on their genetic population

Attempts to understand the role of aneuploidy in tumorigenesis have been hampered by conflicting results. Now, two new mouse models described in Genes and Development provide evidence that chromosome instability-induced aneuploidy drives T cell lymphomagenesis.

Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended

Transposable elements (TEs) promote genetic innovation but also threaten genome stability. Despite multiple layers of host defence, TEs actively shape mammalian-specific developmental processes, particularly during pre-implantation and extra-embryonic development and at the maternal–fetal interface. Here, we review how TEs influence mammalian genomes both directly by providing the raw material for

Interpreting the effects of genetic variants is key to understanding individual susceptibility to disease and designing personalized therapeutic approaches. Modern experimental technologies are enabling the generation of massive compendia of human genome sequence data and associated molecular and phenotypic traits, together with genome-scale expression, epigenomics and other functional genomic data

A new method called CIM-seq analyses pairwise co-occurrences of cell types across multiplets to identify cells that are in physical contact with each other in intact tissues.

A recent study has analysed publicly available long-read sequencing data to characterize human-specific variable number tandem repeats at high resolution.

Kim et al. present a drosophilid genome resource comprising 101 de novo genome assemblies from 93 drosophilid species obtained by nanopore sequencing.

Genome-wide association studies (GWAS) have revealed important biological insights into complex diseases, which are broadly expected to lead to the identification of new drug targets and opportunities for treatment. Drug development, however, remains hampered by the time taken and costs expended to achieve regulatory approval, leading many clinicians and researchers to consider alternative paths to

A study in Current Biology reports the retrieval of genome-scale information for human, wolf (Canis lupus) and bison (Bison bonasus) by shotgun sequencing and genomic analysis of a sediment sample.

A new report introduces xPore, a computational method and statistical framework for the analysis of differential RNA modifications from nanopore direct RNA sequencing data.

Juliusdottir et al. use pedigree data to dissect the contributions of parental and fetal genomes to fetal growth and adult disease.

A recent study analysing UK Biobank data provides a systematic resource of shared genetic predispositions to co-existing common diseases.

Capturing rare protein-coding variation by whole-exome sequencing in large and diverse population samples can help identify large-effect associations and drug targets, suggest two recent publications.

A new study by Ahn et al. shows that chimeric proteins containing intrinsically disordered regions mediate oncogenesis by inducing liquid–liquid phase separation and thereby affecting chromatin conformation and transcription.

Incorporating genomics more widely into cancer screening and management will help to tackle the mortality gap between Black and white patients with cancer. Here, we emphasize the role of genomics as a tool to promote health equity in cancer. In this Comment, Balogun and Olopade highlight opportunities and initiatives for incorporating genomics into cancer management to promote health equity.

Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering include the development of cells that function in biological samples or within the body as minimally invasive diagnostics or theranostics for the real-time regulation of complex diseased states. Ex vivo and in vivo cell-based biosensors

Substance use disorders (SUDs) are conditions in which the use of legal or illegal substances, such as nicotine, alcohol or opioids, results in clinical and functional impairment. SUDs and, more generally, substance use are genetically complex traits that are enormously costly on an individual and societal basis. The past few years have seen remarkable progress in our understanding of the genetics

A study in the American Journal of Human Genetics shows that using the GRCh37 versus GRCh38 version of the human reference genome makes a meaningful difference to the calling of human genetic variants, with implications for research-based and clinical-based human sequencing studies.

The RNA Atlas is reported in Nature Biotechnology. It provides a global view of human RNAs, including thousands of newly characterized non-coding RNAs.

In a paper in Nature, Hua et al. report the Micro-Capture-C method for near-base-pair resolution characterization of chromosomal interactions in mammalian cells.

A study in Cell describes the discovery of a conserved set of small non-coding RNAs that are glycosylated in diverse cell types. These glycoRNAs are found at the surface of cells, where they can participate in extracellular interactions.

Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology

Despite years of active research into the role of DNA repair and replication in mutagenesis, surprisingly little is known about the origin of spontaneous human mutation in the germ line. With the advent of high-throughput sequencing, genome-scale data have revealed statistical properties of mutagenesis in humans. These properties include variation of the mutation rate and spectrum along the genome

Single-cell RNA sequencing (scRNA-seq) identifies cell subpopulations within tissue but does not capture their spatial distribution nor reveal local networks of intercellular communication acting in situ. A suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding

All organisms produce specialized organic molecules, ranging from small volatile chemicals to large gene-encoded peptides, that have evolved to provide them with diverse cellular and ecological functions. As natural products, they are broadly applied in medicine, agriculture and nutrition. The rapid accumulation of genomic information has revealed that the metabolic capacity of virtually all organisms

Despite being collectively among the most frequent congenital developmental conditions worldwide, differences of sex development (DSD) lack recognition and research funding. As a result, what constitutes optimal management remains uncertain. Identification of the individual conditions under the DSD umbrella is challenging and molecular genetic diagnosis is frequently not achieved, which has psychosocial

A broad spectrum of rare disease presentations can now be investigated by analysing mitochondrial DNA (mtDNA) variants from whole-genome sequencing (WGS) data. However, mtDNA mutations may cause unanticipated, extended phenotypes and have reproductive implications. We recommend that these be considered by patients and clinicians before embarking on WGS. Variants in mitochondrial DNA (mtDNA), which

Long-read sequencing technologies have now reached a level of accuracy and yield that allows their application to variant detection at a scale of tens to thousands of samples. Concomitant with the development of new computational tools, the first population-scale studies involving long-read sequencing have emerged over the past 2 years and, given the continuous advancement of the field, many more are

Two studies report the successful application of CRISPR adenine base editors for in vivo genome editing of a disease-related gene in non-human primates.

Evidence for a biparental mode of mitochondrial DNA (mtDNA) inheritance has been sparse and remains controversial. Recent studies using a range of complementary techniques do not support paternal transmission of mtDNA and highlight the co-amplification of rare, concatenated nuclear mtDNA segments as a technical artefact that may explain previous observations. This Comment discusses recent studies supporting

In this Journal Club, Irene Bozzoni spotlights two Nature publications that reported the occurrence of thousands of circular RNAs in eukaryotes.

The Vertebrate Genomes Project, which aims to produce high-quality reference genomes for all 71,657 living and named vertebrate species, reports the generation of high-quality genome assemblies for the first 16 species and describes the biological findings that these genomes have informed.

Elaine Mardis highlights a publication that served as a fundamental source of inspiration for the field of immunogenomics, setting the stage for neoantigen discovery.

Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental

The temporal coordination of events at cellular and tissue scales is essential for the proper development of organisms, and involves cell-intrinsic processes that can be coupled by local cellular signalling and instructed by global signalling, thereby creating spatial patterns of cellular states that change over time. The timing and structure of these patterns determine how an organism develops. Traditional

During development, cell competition causes apoptosis of cells with abnormal ribosomal protein profiles. Ji et al. show that this same mechanism also deletes aneuploid cells and that the deleted cell populations mainly have altered ribosomal protein gene dosages.

Schep et al. show that non-homologous end joining is strongly favoured in euchromatin, whereas single-stranded template repair is moderately preferred in heterochromatin. Importantly, heterochromatin features that promote microhomology-mediated end joining also decrease Cas9 efficiency.

Human telomerase reverse transcriptase (hTERT) activity is tightly controlled. This report shows that hTERT is primarily regulated by alternative splicing; skipping of exon 2 triggers decay of TERT mRNA in differentiated cells and its retention promotes telomere maintenance in pluripotent cells.

Deborah Charlesworth reflects on a 1970 publication by Haskins et al., a study on guppy Y chromosomes that beautifully demonstrates the use of classical genetics and remains intriguing to this day.

Assembly and publication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome in January 2020 enabled the immediate development of tests to detect the new virus. This began the largest global testing programme in history, in which hundreds of millions of individuals have been tested to date. The unprecedented scale of testing has driven innovation in the strategies, technologies

A new study in Science reports the extraction and analysis of ancient hominid nuclear DNA from Paleolithic sediments. This advance paves the way to a fuller picture of human evolution by bypassing the dependency on rare skeletal remains.

Epigenetics has enriched human disease studies by adding new interpretations to disease features that cannot be explained by genetic and environmental factors. However, identifying causal mechanisms of epigenetic origin has been challenging. New opportunities have risen from recent findings in intra-individual and cyclical epigenetic variation, which includes circadian epigenetic oscillations. Cytosine

Cisca Wijmenga reflects on a seminal publication by Houwen et al. that set the stage for genome-wide association studies and inspired her to dedicate her lab to complex trait genetics.

Single-cell omics is transforming our understanding of cell biology and disease, yet the systems-level analysis and interpretation of single-cell data faces many challenges. In this Perspective, we describe the impact that fundamental concepts from statistical mechanics, notably entropy, stochastic processes and critical phenomena, are having on single-cell data analysis. We further advocate the need

Xia et al. highlight an unexpected horizontal gene transfer event, whereby the sweet potato whitefly has harnessed a host plant detoxification mechanism to resist its defences.

A Correction to this paper has been published: https://doi.org/10.1038/s41576-021-00361-9.

Our Journal Club articles explore historical scientific publications that have served as inspiration, be it for their originality, importance, interdisciplinary interest, elegance or surprising conclusions. From the June 2021 issue onwards, Nature Reviews Genetics will publish Journal Club articles, which explore a historical scientific publication that has served as inspiration to the author.

Qifa Zhang describes how a 2008 publication in Nature Biotechnology on transgenic purple tomatoes inspired him to tackle food security by improving the nutrient and culinary value of black rice.