Reviews & Analysis

DNA and histone modifications undergo extensive reprogramming to reset the epigenomic state between generations. This Review discusses the mechanisms and consequences of epigenetic reprogramming during plant sexual reproduction. Despite various similarities to the equivalent process in mammals, a key difference is the seemingly incomplete reprogramming of plant epigenomes, which has implications for evolution and transgenerational epigenetic inheritance.

This Review introduces the biological barriers to gene deliveryin vivoand discusses recent advances in material sciences, nanotechnology and nucleic acid chemistry that have yielded promising non-viral systems for the delivery of DNA, mRNA, small interfering RNAs and microRNAs, some of which are currently undergoing testing in clinical trials.

This Review discusses the main experimental approaches for microRNA (miRNA) target identification, as well as the modulators and the consequences of miRNA–target interactions. It also highlights the role of computational modelling in furthering the conceptual understanding of miRNA functions in gene regulatory networks.

The field of cancer genomics has been transformed by recent advances in sequencing and the development of new computational methods. This Review outlines the available cancer genomics software and describes recent insights gained from the application of these tools.

Among rodent species, there is a wide diversity in lifespans and cancer susceptibilities, which makes comparative studies of rodents an attractive strategy for identifying molecular mechanisms that underlie ageing and cancer. This Review describes the various biological insights provided by comparative rodent genomics, including those from whole-genome sequencing of long-lived and highly cancer-resistant species. Such progress has potential implications for understanding and modulating human disease.

Mutagenic processes leave characteristic imprints on the cancer genome that can help to identify the underlying DNA damaging components as well as DNA repair and replicative pathways that are active or disrupted. This Review discusses these mutational signatures according to different classes of mutations and summarizes how different components contribute mechanistically to produce each signature type.

Imprinted genes influence a wide range of biological processes, the effects of which extend from prenatal stages to adulthood. This Review discusses the role of imprinted genes, with a focus on postnatal and adult phenotypes, and their contribution to common diseases such as intrauterine growth restriction, obesity, psychiatric disorders and cancer.

The role of telomeric factors as guardians of chromosome ends from threats to genome integrity (such as degradation and inappropriate DNA damage response activation) has long been appreciated. This Review discusses the extratelomeric activity of these factors and how they can regulate the transcription of genes involved in metabolism, immunity and differentiation.

Gene-regulatory DNA elements control complex spatiotemporal patterns of gene expression, and alterations to these sequences are commonly associated with inter-individual phenotypic variation and human disease. This Review discusses our latest understanding of how different layers of information in these sequences control the binding of regulators and influence gene expression outcomes.

A central topic in biology concerns how genotypes determine phenotypes and functions of organisms that affect their evolutionary fitness. This Review discusses recent advances in the development of empirical fitness landscapes and their contribution to theoretical analyses of the predictability of evolution.

In this Opinion article, the authors highlight the potential of genome engineering for the study of evolution and focus on microbial systems. They discuss the prospects and problems of the emerging field of evolutionary genome engineering, and pinpoint how a combination of genome engineering and laboratory evolution can shed light on evolutionary forces.

Although gene delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective for numerous clinical gene therapy applications, many challenges remain. Recent advances in AAV vector development through rational design and directed evolution, as well as in the design of novel genetic cargoes, promise to extend clinical successes of AAV-mediated gene therapy.

Recent technological advances have enabled the probing of RNA structure across the transcriptomes of various speciesin vitro and in vivo. This Review discusses our latest understanding of how RNA structure influences various steps of gene expression, including translation, mRNA localization and microRNA-mediated gene regulation.

RNA-directed DNA methylation (RdDM) is a major mechanism of transcriptional gene silencing in plants that is mediated through small interfering RNAs (siRNAs) and plant-specific RNA polymerases. This Review summarizes our latest understanding of RdDM, including its genomic targets, molecular mechanisms (such as emerging non-canonical pathways) and diverse biological roles.

Data sharing in genetics is essential to ensure research progress. However, concerns about the impact on privacy of data originators have been raised. This Review summarizes privacy breaching strategies and potential mitigation methods for privacy-preserving dissemination of sensitive data, and highlights different cases that are relevant to genetic applications.

Discoveries over the past decade portend a paradigm shift in molecular biology; evidence suggests that RNA is not only functional as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression. This Timeline article surveys the emergence of the previously unsuspected world of regulatory RNA from a historical perspective.

The impact of various infectious agents on human survival and reproduction over thousands of years has exerted selective pressure on numerous regions of the human genome. This Review describes how such signatures of selection can be detected and integrated with data from complementary approaches, such as genome-wide association studies, to provide biological insights into host–pathogen interactions.

This Review discusses the principles and applications of significance testing and power calculation, including recently proposed gene-based tests for rare variants.

The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. This Review discusses the causes and consequences of variability in X-linked gene expression.

Whole-genome assemblies of humans and non-human primates are yielding data on the evolutionary origins of the human genome, as well as insights into genetic similarities and differences between species used as models for disease-related research. This Review discusses current knowledge and opportunities for comparative primate genomics created by recent advances in genome sequencing technologies.