Review Articles

The rising human population and climate instability are putting unprecedented pressure on global agricultural practices. This Review describes the diverse mechanisms by which plants tolerate various stresses, such as flooding, drought, toxins, salinity and temperature extremes. The authors focus on how the genetic loci that underlie these survival and tolerance traits can be introgressed into current crops to improve yield stability.

The evolution of genes is influenced by regional variation in mutation rates (RViMR). Chromatin organization affects RViMR, although the correlation between chromatin state and mutation types and rates is complex. This Review describes recent research on RViMR and chromatin organization, and the emerging findings from investigations of both germline and somatic mutations.

Rett syndrome is a neurological disorder associated with mutations in the X-linked geneMECP2(methyl-CpG-binding protein 2). This Review details emerging insights into the link between the functions of MeCP2 and the pathogenesis of Rett syndrome.

Genetic variation in gene expression among individuals is an important contributor to differences in organismal phenotypes. This Review describes key concepts of such variation and provides an update on recent research on the effects of regulatory variants on the transcriptome, proteome and complex traits, including human disease risk.

Synthetic biology approaches to characterize gene regulation have largely used transcription factor circuits in bacteria. However, the multilayered regulation of genes by chromatin in eukaryotes provides opportunities for more sophisticated control of gene expression. This Review describes diverse approaches for engineering eukaryotic chromatin states, the insights gained into physiological gene regulation principles, and the broad potential applications throughout biomedical research and industry.

The use of mathematical modelling to elucidate genetic, molecular and cellular processes is an integral part of systems biology. This Review presents the main methods to model and simulate molecular and gene networks (kinetic and logic modelling), describes their inherent advantages and limitations, and highlights recent developments that reveal the potential of hybrid approaches.

High-throughput RNA sequencing (RNA-seq) is a powerful method for transcriptome-wide analysis that has recently been applied to single cells. This Review discusses the analytical and computational challenges of processing and analysing single-cell RNA-seq data, paying special consideration to differences relative to the analysis of RNA-seq data generated from bulk cell populations and discussing how single-cell-specific biological insights can be obtained.

Integrating multiple data types can be substantially more informative than analysing data sets separately, and methods to combine data sets are now emerging. This Review outlines the current approaches for data integration and the various strengths and weaknesses of these strategies. The analytical challenges that emerge with data sets of this magnitude are also described, and the authors provide their perspective on how such systems genomic analyses might develop in the future.

Small and long non-coding RNAs have emerged as key regulators of gene expression through their direct and indirect actions on chromatin. This Review describes how RNAs form powerful surveillance systems that detect and silence inappropriate transcription events, and how such systems provide a memory of these events via self-reinforcing epigenetic loops.

This Review describes our latest understanding of the range of functions of tRNAs. Emerging roles include the tight regulation of tRNA biogenesis to meet the translational needs of different cell types, cleavage and covalent modification of tRNAs in stress signalling, and diverse mechanistic links to various diseases.

Large-scale genetic perturbation screens have been central to many biological discoveries. This Review outlines the recent advances in the quantification of various perturbations across large numbers of single cells simultaneously and describes the use of genetic perturbation screens to infer functional interactions between genes and phenotypes.

Mendelian conditions, which are caused by dysfunction of a single gene, illustrate how the availability of the human genome sequence and tools for interrogating individual genomes can provide insights into disease. In this Review, cystic fibrosis is presented as an example of how genetics can continuously inform clinical research and practice.

Relatedness has traditionally been defined using pedigree-based measures, but these have serious deficiencies. With genome-wide data, SNP-based measures can now be used to directly measure genome similarity, a more useful concept than relatedness. This Review outlines ways to evaluate measures of genome similarity.

The RNA World concept is the idea that billions of years ago — before current life based on DNA, RNA and proteins — the primary living substance was RNA or something chemically similar. This Review highlights the challenges and solutions of this point of view, particularly for the synthesis and replication of RNA, and how various types of molecular cooperation probably had important roles.

Various small molecules, including numerous anticancer agents, act by targeting DNA or protein components of chromatin. This Review describes how various complementary technologies use high-throughput sequencing to delineate drug responses, from identifying the genomic binding sites of drugs or their targets, to the ensuing changes to chromatin states and gene expression. These insights should facilitate the rational use of these therapies.

The resolution of epigenomic profiling has been vastly augmented with the adoption of new approaches to interrogate varied features of the epigenome. This Review describes these techniques and outlines the ways in which these genome-wide tools can be used to examine the epigenome.

This Review provides insights obtained from comparative transcriptomic studies of mammalian species. The dynamics of gene expression evolution in coding and non-coding genes, as well as the regulatory basis of transcriptome evolution and future research avenues, are discussed.

Various bacterial and eukaryotic microorganisms engage in interactions with plant hosts, ranging from co-evolutionary arms races between phytopathogens and their hosts to the beneficial effects of mutualistic microorganisms. This Review discusses how next-generation sequencing of microbial isolates and environmental samples has provided insights into the mechanisms and genome-wide evolution of pathogenesis in phytopathogens, as well as a more global understanding of plant-associated microbial communities.

This Review describes how whole-genome sequencing of pooled DNA from many individuals (Pool-seq) is an economical alternative to sequencing the genomes of individuals separately. The authors outline the strengths and pitfalls of Pool-seq, and provide example applications across diverse species and biological questions.

Next-generation sequencing methods can be used to examine features of chromatin biology, although the outputs of these methods can be subject to various potential biases. This Review describes the ways in which biases can be introduced to such experiments and outlines methods to detect and mitigate their effect.