Two papers in Cell report large-scale genome-wide association studies that provide new insights into the genetic architecture of haematopoietic phenotypes and emphasize the importance of large, diverse data sets.

In Africa, there is a disparity in ethics and permission requirements for molecular research on samples from living people versus ancient DNA. At the precipice of the archaeogenomics revolution, heritage agencies require updated policies and procedures for genetic and genomic research on African ancient DNA.

As Nature Reviews Genetics turns 20 years, the editors embrace the opportunity to pause and reflect on the past, take stock of the present and look to the future. Please join us in celebrating our Anniversary issue.

Molecular inputs to chromatin via cellular metabolism are modifiers of the epigenome. These inputs — which include both nutrient availability as a result of diet and growth factor signalling — are implicated in linking the environment to the maintenance of cellular homeostasis and cell identity. Recent studies have demonstrated that these inputs are much broader than had previously been known, encompassing

A study in Cell presents a new approach that increases resolution and throughput compared with existing imaging methods and provides insights into the relationship between transcription and the 3D genome.

Studies in diverse biological systems have indicated that host–parasite co-evolution is responsible for the extraordinary genetic diversity seen in some genomic regions, such as major histocompatibility (MHC) genes in jawed vertebrates and resistance genes in plants. This diversity is believed to evolve under balancing selection on hosts by parasites. However, the mechanisms that link the genomic signatures

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Proteomic analysis of cells, tissues and body fluids has generated valuable insights into the complex processes influencing human biology. Proteins represent intermediate phenotypes for disease and provide insight into how genetic and non-genetic risk factors are mechanistically linked to clinical outcomes. Associations between protein levels and DNA sequence variants that colocalize with risk alleles

In celebration of the 20th anniversary of Nature Reviews Genetics, we asked 12 leading researchers to reflect on the key challenges and opportunities faced by the field of genetics and genomics. Keeping their particular research area in mind, they take stock of the current state of play and emphasize the work that remains to be done over the next few years so that, ultimately, the benefits of genetic

A recent study combines CRISPR-based perturbation with single-cell RNA sequencing to characterize the roles of epigenome regulator proteins in controlling cell fate and identity during embryonic development.

A new study in Science uses chromatin accessibility profiles to reveal gene regulatory alterations associated with genetic variants in neuropsychiatric disease.

Reference-quality genomes for six bat species published in Nature yield insights into the evolutionary origins of bats and the molecular basis of adaptive traits involved in immunity and sensory perception.

Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and interactions with the microenvironment. Therefore

A study in PNAS describes a maternal-effect killer supergene that regulates social behaviour in Alpine silver ants. Queens carrying the ‘killer’ haplotype fail to produce live progeny homozygous for the alternative haplotype, ensuring all colonies adopt a multiple-queen, rather than single-queen, social structure.

The growth and survival of cells within tissues can be affected by ‘cell competition’ between different cell clones. This phenomenon was initially recognized between wild-type cells and cells with mutations in ribosomal protein (Rp) genes in Drosophila melanogaster. However, competition also affects D. melanogaster cells with mutations in epithelial polarity genes, and wild-type cells exposed to ‘super-competitor’

Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects on the promises that this voyage of discovery bore. Its success should be measured by how this project transformed the rules of research, the way of practising biological discovery and the ubiquitous digitization of biological science. Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A study in Cell introduces memory sequencing (MemorySeq), a method for identifying genes that are highly and heritably expressed over multiple cell divisions. These expression patterns can reveal cellular subpopulations with distinct phenotypes, such as drug resistance.

All organisms must safeguard the integrity of their DNA to avoid deleterious consequences of genome instability, which have been linked to human diseases such as autoimmune disorders, neurodegenerative diseases and cancer. Traditionally, genome maintenance has been viewed largely in terms of DNA–protein interactions. However, emerging evidence points to RNA as a key modulator of genome stability, with

A study in Nature describes the assembly of a human genome with greater continuity than the current reference genome, as well as the assembly of a complete human X chromosome. These assemblies were achieved by combining data generated by different long-read sequencing technologies.

Gene expression involves transcription, translation and the turnover of mRNAs and proteins. The degree to which protein abundances scale with mRNA levels and the implications in cases where this dependency breaks down remain an intensely debated topic. Here we review recent mRNA–protein correlation studies in the light of the quantitative parameters of the gene expression pathway, contextual confounders

Data sharing anchors reproducible science, but expectations and best practices are often nebulous. Communities of funders, researchers and publishers continue to grapple with what should be required or encouraged. To illuminate the rationales for sharing data, the technical challenges and the social and cultural challenges, we consider the stakeholders in the scientific enterprise. In biomedical research

A study in Nature analysing genome-wide variation in individuals from islands across Polynesia reports evidence of admixture with Native Americans related to Indigenous inhabitants of northern South America.

Epigenetic clocks translate the DNA methylome into a biological age but usually work only within a species. Now, a study in Cell Systems reports a cross-species epigenetic clock that works across a number of mammals, including humans, dogs and mice.

Despite enormous progress in understanding the fundamentals of bacterial gene regulation, our knowledge remains limited when compared with the number of bacterial genomes and regulatory systems to be discovered. Derived from a small number of initial studies, classic definitions for concepts of gene regulation have evolved as the number of characterized promoters has increased. Together with discoveries

A new study in Nature Methods presents the ‘ZipSeq’ spatial transcriptomics approach, whereby patterned illumination is used to print barcodes onto chosen tissue regions.

Structural variants have proved difficult to characterize using traditional sequencing approaches. In two new studies in Cell, the authors demonstrate the use of pan-genome approaches to identify and explore the impact of structural variants in crop genomes and reveal variants linked to specific agronomic traits.

Now more than ever, digital applications are essential to accessing genetics services and optimizing their delivery. At this watershed moment, digital solutions must be balanced with the merits of human interaction, without compromising quality or exacerbating existing genomic and technological disparities. As highlighted by the COVID-19 pandemic, digital solutions are becoming essential for the provision

Most adaption processes have a polygenic genetic basis, but even with the recent explosive growth of genomic data we are still lacking a unified framework describing the dynamics of selected alleles. Building on recent theoretical and empirical work we introduce the concept of adaptive architecture, which extends the genetic architecture of an adaptive trait by factors influencing its adaptive potential

Three new studies in Nature Biotechnology combine the adenine and cytosine deaminase activities of single base editors to generate dual base editor systems for combinatorial editing in human cells.

Transposable elements (TEs) are insertional mutagens that contribute greatly to the plasticity of eukaryotic genomes, influencing the evolution and adaptation of species as well as physiology or disease in individuals. Measuring TE expression helps to understand not only when and where TE mobilization can occur but also how this process alters gene expression, chromatin accessibility or cellular signalling

A study in Nature describes a new method for studying variation in meiosis. Sperm-seq is a single-cell sequencing approach that enables genome-wide analysis of multiple meiotic phenotypes in thousands of sperm simultaneously.

Cancer ‘genetic dependencies’ — genes whose products are essential for cancer cell fitness — are promising targets for therapeutic development. However, recent evidence has cast doubt on the validity of several putative dependencies that are currently being targeted in cancer clinical trials, underscoring the challenges inherent in correctly identifying cancer-essential genes. Here we review several

It has been 10 years since the introduction of modern transposon-insertion sequencing (TIS) methods, which combine genome-wide transposon mutagenesis with high-throughput sequencing to estimate the fitness contribution or essentiality of each genetic component in a bacterial genome. Four TIS variations were published in 2009: transposon sequencing (Tn-Seq), transposon-directed insertion site sequencing

Genomic imprinting and X-chromosome inactivation (XCI) are classic epigenetic phenomena that involve transcriptional silencing of one parental allele. Germline-derived differential DNA methylation is the best-studied epigenetic mark that initiates imprinting, but evidence indicates that other mechanisms exist. Recent studies have revealed that maternal trimethylation of H3 on lysine 27 (H3K27me3) mediates

Regeneration is the process by which organisms replace lost or damaged tissue, and regenerative capacity can vary greatly among species, tissues and life stages. Tissue regeneration shares certain hallmarks of embryonic development, in that lineage-specific factors can be repurposed upon injury to initiate morphogenesis; however, many differences exist between regeneration and embryogenesis. Recent

Over the past decade, long-read, single-molecule DNA sequencing technologies have emerged as powerful players in genomics. With the ability to generate reads tens to thousands of kilobases in length with an accuracy approaching that of short-read sequencing technologies, these platforms have proven their ability to resolve some of the most challenging regions of the human genome, detect previously

During ageing, many normal human tissues become a patchwork of mutant clones. Colom et al. show that, in mutagenized mouse oesophageal epithelium, this mutational landscape arises through cell competition, with clone fitness determined by the genotype of their neighbours.

A collection of seven articles from the gnomAD consortium, published in Nature, Nature Medicine and Nature Communications, showcases analyses of global human genetic variation in coding and non-coding genomic regions across this data set.

Recombination is a central biological process with implications for many areas in the life sciences. Yet we are only beginning to appreciate variation in the recombination rate along the genome and among individuals, populations and species. Spurred by technological advances, we are now able to bring variation in this key biological parameter to centre stage. Here, we review the conceptual implications

The self-renewal capacity of multipotent haematopoietic stem cells (HSCs) supports blood system homeostasis throughout life and underlies the curative capacity of clinical HSC transplantation therapies. However, despite extensive characterization of the HSC state in the adult bone marrow and embryonic fetal liver, the mechanism of HSC self-renewal has remained elusive. This Review presents our current

A study in Cell Reports describes a machine learning model, named Xpresso, that uses genomic sequence to predict mRNA steady-state abundance.

A new study in Cell describes the CRISPR array repair lineage tracing (CARLIN) engineered mouse line that genomically encodes all the components for CRISPR-based lineage tracking at single-cell resolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Two papers in Nature Chemical Biology describe new methods for transcriptome-mapping of N6-methyladenosine (m6A), a covalent modification of RNA. In m6A-SEAL, modified adenosines can be tagged with different functional groups for different applications, whereas m6A-label-seq uses metabolic labelling to achieve single-nucleotide resolution.

Knowing phylogenetic relationships among species is fundamental for many studies in biology. An accurate phylogenetic tree underpins our understanding of the major transitions in evolution, such as the emergence of new body plans or metabolism, and is key to inferring the origin of new genes, detecting molecular adaptation, understanding morphological character evolution and reconstructing demographic

A study reports on the suitability of the yeast Saccharomyces cerevisiae as a platform for the assembly and maintenance of diverse RNA virus genomes, including SARS-CoV-2.

Coloration is an easily quantifiable visual trait that has proven to be a highly tractable system for genetic analysis and for studying adaptive evolution. The application of genomic approaches to evolutionary studies of coloration is providing new insight into the genetic architectures underlying colour traits, including the importance of large-effect mutations and supergenes, the role of development

Two studies in Molecular Cell report fine-scale structural profiles of mammalian genomes using Micro-C, indicating that fine chromosomal structure is regulated by diverse transcription-related features.

Just as humans thrive from being part of a community, genetics and genomics benefit from interdisciplinary collaboration and knowledge integration.

Comparative studies struggle with the challenge of balancing technical properties with the requirement of obtaining samples from multiple species. Guidelines are needed to minimize the effect of confounders and increase the robustness of the inference. We argue for the paramount importance of extensive record keeping and reporting. Comparative studies struggle to balance technical properties with the