Age is the key risk factor for diseases and disabilities of the elderly. Efforts to tackle age-related diseases and increase healthspan have suggested targeting the ageing process itself to ‘rejuvenate’ physiological functioning. However, achieving this aim requires measures of biological age and rates of ageing at the molecular level. Spurred by recent advances in high-throughput omics technologies

In genomics, both the denomination ‘African’ as well at the ethnic groups living in Africa have been treated as true biological identities. Yet, similar to race, these population groupings too are social constructs. We argue that using African ethnicities as population categories in genomics research is uninformed and propose an Africa-oriented humanities research agenda to critique and support genomic

Polycomb group (PcG) proteins are crucial chromatin regulators that maintain repression of lineage-inappropriate genes and are therefore required for stable cell fate. Recent advances show that PcG proteins form distinct multi-protein complexes in various cellular environments, such as in early development, adult tissue maintenance and cancer. This surprising compositional diversity provides the basis

tRNAs are key adaptor molecules that decipher the genetic code during translation of mRNAs in protein synthesis. In contrast to the traditional view of tRNAs as ubiquitously expressed housekeeping molecules, awareness is now growing that tRNA-encoding genes display tissue-specific and cell type-specific patterns of expression, and that tRNA gene expression and function are both dynamically regulated

With age, somatic mutations accumulate in the genome of healthy individuals, but the functional outcome of this increased mutational load has been unclear. Recent sequencing data support a functional role for somatic mutations in ageing and age-associated diseases. Somatic mutations accumulate with age in the genome of healthy individuals. Franco and Eriksson posit that recent sequencing data indicate

Gregor Johann Mendel, the ‘father of modern genetics’, was born 200 years ago, on 20 July 1822. In commemoration of this milestone, in our July issue we reflect on his legacy and the field’s responsibility around potential uses and abuses of genetics and genomics research. In this Editorial, we reflect on the field’s responsibility around the potential uses and abuses of genetics and genomics research

In this Journal Club, Itay Tirosh highlights a 2011 publication by Gupta et al., which showed that cells undergo frequent stochastic transitions between distinct states in breast cancer cell lines.

Gegenhuber et al. now show that, in mice, a neonatal surge in oestradiol activates oestrogen receptor-α to drive a sustained male-typical gene expression programme that determines brain sexual differentiation.

In celebrating the bicentenary of Gregor Mendel’s birth, we reflect on progress and future directions in the application of genetics and genomics to delivering a cure for sickle cell disease, a classic Mendelian disorder that affects 5 million people globally, most of whom are in Africa. To mark the bicentenary of Gregor Mendel’s birth, the authors reflect on progress in the application of genetics

Cells and tissues generate and are exposed to various mechanical forces that act across a range of scales, from tissues to cells to organelles. Forces provide crucial signals to inform cell behaviour during development and adult tissue homeostasis, and alterations in forces and in their downstream mechanotransduction pathways can influence disease progression. Recent advances have been made in our

A recent study reports the development of Stereo-seq (spatial enhanced resolution omics-sequencing) and its application to generate a spatiotemporal transcriptomic atlas of mouse organogenesis.

July 2022 will see the bicentenary of the birth of Gregor Mendel, often hailed as the ‘father of modern genetics’. To mark the occasion, I retrace Mendel’s origins, revisit his famous study ‘Experiments in plant hybridization’, and reflect on the revolutionary implications of his work and scientific legacy that continues to shape modern biomedicine to this day.

A new study presents GLUE (graph-linked unified embedding), a generalizable computational framework for integrating unpaired single-cell multi-omics data and for inferring regulatory interactions.

Gene loss is followed by the rapid emergence of new phenotypes owing to compensatory evolution, finds a recent study using experimental evolution of budding yeast lineages.

Levo et al. used quantitative single-cell live imaging to analyse the transcriptional dynamics of fly paralogues separated by long genomic distances, to determine whether they are co-regulated.

Genome-wide association studies using large-scale genome and exome sequencing data have become increasingly valuable in identifying associations between genetic variants and disease, transforming basic research and translational medicine. However, this progress has not been equally shared across all people and conditions, in part due to limited resources. Leveraging publicly available sequencing data

Lillian Musila highlights a paper by Quick et al., which reported the use of portable nanopore sequencing for on-site, real-time genomic surveillance during the 2014–2016 Ebola virus epidemic.

Elizabeth Mason recalls a seminal study by Raj et al., who used single-molecule approaches to expose principles governing how genes in a network cooperate to buffer perturbation while maintaining essential cellular functions.

Careers in biomedicine can take many forms, and one common career decision facing scientists is whether to pursue jobs in academia or industry. In this Viewpoint article, four leading scientists who have spent time in both academia and industry provide their perspectives on both types of workplace, such as whether the environments are really as distinct as they are often perceived to be, as well as

Developed at a time when the basic molecular and cellular elements of inheritance were yet to be identified, the concepts of dominance and recessiveness are at the core of the connection between genotype and phenotype in diploid organisms. On the occasion of Gregor Mendel’s 200th birthday, we reflect on the history of the terms dominant and recessive, and their current use in medical genetics. On the

Over time, the human DNA methylation landscape accrues substantial damage, which has been associated with a broad range of age-related diseases, including cardiovascular disease and cancer. Various age-related DNA methylation changes have been described, including at the level of individual CpGs, such as differential and variable methylation, and at the level of the whole methylome, including entropy

Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different

In six new studies published in Science, the Telomere-to-Telomere (T2T) Consortium reports the assembly and initial characterization of the final, previously unresolved 8% of the human genome.

Dimple Notani highlights a 1981 paper by Banerji et al. that describes the discovery of viral enhancer elements and that continues to shape her research today.

The mitochondrial genome encodes core subunits of the respiratory chain that drives oxidative phosphorylation and is, therefore, essential for energy conversion. Advances in high-throughput sequencing technologies and cryoelectron microscopy have shed light on the structure and organization of the mitochondrial genome and revealed unique mechanisms of mitochondrial gene regulation. New animal models

Determining the transmissibility, prevalence and patterns of movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is central to our understanding of the impact of the pandemic and to the design of effective control strategies. Phylogenies (evolutionary trees) have provided key insights into the international spread of SARS-CoV-2 and enabled investigation of individual

A paper in Nature Biotechnology describes epigenetic expression inference from cfDNA-sequencing (EPIC-seq), and demonstrates its use for non-invasive classification of cancers.

A paper in Molecular Cell reports EpiDamID, a new tool for simultaneously profiling transcription and histone post-translation modifications in single cells.

A recent study in Cell describes a developmentally important liquid-to-solid phase transition involving oskar ribonucleoprotein granules in Drosophila melanogaster oocytes.

In this Journal Club, Ambroise Wonkam describes how whole-exome sequencing of genetically diverse populations of African ancestry can provide insights into both complex and Mendelian disease.

In this Journal Club, Yukinori Okada recalls a 1987 publication that introduced a simple conceptual framework, the shared epitope hypothesis, to explain the genetic risk of rheumatoid arthritis conferred by HLA-DRB1 alleles.

In this Journal Club article, Geoff Faulkner discusses how a ground-breaking study of LINE-1 mobility in human genomes demonstrated not just a role in disease but also molecular details of the mechanisms of retrotransposition.

Public health strategies aimed at disease prevention or early detection and intervention have the potential to advance human health worldwide. However, their success depends on the identification of risk factors that underlie disease burden in the general population. Genome-wide association studies (GWAS) have implicated thousands of single-nucleotide polymorphisms (SNPs) in common complex diseases

A new study in Science uses massively parallel reporter assays to show that human genetic associations are often driven by multiple genetic variants acting together within an associated locus.

In this Journal Club article, Yana Bromberg discusses an early application of machine learning for protein structure prediction — a paper that shaped her career. It illustrates the value of ensuring that machine learning approaches are rooted in known biological principles.

The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have

Much has been learned since the early 1960s about histone post-translational modifications (PTMs) and how they affect DNA-templated processes at the molecular level. This understanding has been bolstered in the past decade by the identification of new types of histone PTM, the advent of new genome-wide mapping approaches and methods to deposit or remove PTMs in a locally and temporally controlled manner

A paper in Science describes a system in synthetic yeast chromosomes in which the properties of genetic sequences change depending on the neighbouring transcriptional activity.

DNA methylation data have become a valuable source of information for biomarker development, because, unlike static genetic risk estimates, DNA methylation varies dynamically in relation to diverse exogenous and endogenous factors, including environmental risk factors and complex disease pathology. Reliable methods for genome-wide measurement at scale have led to the proliferation of epigenome-wide

A recent study in Nature Genetics investigates the role of DNA replication in cellular plasticity during mouse embryonic development.

Lin et al. explore the impact of evolutionary divergence on de-extinction efforts that use genome editing using the extinct Christmas Island rat.

Omary et al. map shoot-borne root development at single-cell resolution in tomato to identify the origin of shoot-borne roots.

A recent paper in Nature describes how CRISPR-based engineering of wheat confers robust resistance to powdery mildew disease without negatively impacting crop growth and yields.

Carla Daniela Robles-Espinoza celebrates a paper that inspired a new generation of Mexican scientists.

Irene Gallego Romero recalls a landmark publication by Rosenberg et al., which reported on the fine-scale structure within and between human populations.

N6-methyl-2′-deoxyadenosine (6mA or m6dA) has been reported in the DNA of prokaryotes and eukaryotes ranging from unicellular protozoa and algae to multicellular plants and mammals. It has been proposed to modulate DNA structure and transcription, transmit information across generations and have a role in disease, among other functions. However, its existence in more recently evolved eukaryotes remains

The AID/APOBEC polynucleotide cytidine deaminases have historically been classified as either DNA mutators or RNA editors based on their first identified nucleic acid substrate preference. DNA mutators can generate functional diversity at antibody genes but also cause genomic instability in cancer. RNA editors can generate informational diversity in the transcriptome of innate immune cells, and of

Recent developments in a variety of sectors, including health care, research and the direct-to-consumer industry, have led to a dramatic increase in the amount of genomic data that are collected, used and shared. This state of affairs raises new and challenging concerns for personal privacy, both legally and technically. This Review appraises existing and emerging threats to genomic data privacy and

Two new studies of mutations linked to distinct neurological conditions — autism spectrum disorders (ASD) and tuberous sclerosis complex (TSC) — use human brain organoids to identify mutation-driven alterations to cell lineage trajectories during early brain development.

The development of single-cell and spatial transcriptomics methods was instrumental in the conception of the Human Cell Atlas initiative, which aims to generate an integrated map of all cells across the human body. These technology advances are bringing increasing depth and resolution to maps of human organs and tissues, as well as our understanding of individual human cell types. Commonalities as

Two recent studies published in Nature Biotechnology describe the engineering of circularized guide RNAs, which allow for programmable RNA base editing in vivo, with vastly improved editing efficiency and durability.

Michael Purugganan reflects on a 100-year-old publication by Nikolai Vavilov, which postulated a new law of genetics from which key evolutionary insights emerged and which guided future molecular genetic investigations.

Flotte et al. describe the first test of adeno-associated virus-based gene therapy for Tay-Sachs disease in humans. Delivery to the thalamus and cerebrospinal fluid was found to be broadly safe, providing a firm basis for future clinical trials.

Using whole-genome sequencing and haplotype tracking, Viluma et al. show that the small, highly inbred Scandinavian wolf population has lost substantial genetic diversity over a 30-year period. Their findings have important implications for the management and conservation of endangered species.

Kong et al. describe 6mASCOPE, a new approach for both quantifying N6-methyldeoxyadenine (6mA) and discriminating its genomic source. Results indicate that eukaryotic genomes contain low levels of 6mA, with bacterial genomes accounting for the majority of 6mA in some samples.

A study in Nature reconstructs haematopoietic phylogenies and tracks clonal evolutionary dynamics in 12 patients with adult-onset myeloproliferative neoplasms, revealing that initial driver mutations of these cancers often occur during childhood, including in utero.

Genetic variation, which is generated by mutation, recombination and gene flow, can reduce the mean fitness of a population, both now and in the future. This ‘genetic load’ has been estimated in a wide range of animal taxa using various approaches. Advances in genome sequencing and computational techniques now enable us to estimate the genetic load in populations and individuals without direct fitness

In this Journal Club, Itai Yanai discusses key quantitative work characterizing the occurrence and fates of gene duplicates across various species.

New work studying the plant Arabidopsis thaliana shows that patterns of observed sequence variants are primarily influenced by biases in initial mutation occurrences rather than by the subsequent selective pressures.