Primate genomics holds the key to understanding fundamental aspects of human evolution and disease. However, genetic diversity and functional genomics data sets are currently available for only a few of the more than 500 extant primate species. Concerted efforts are under way to characterize primate genomes, genetic polymorphism and divergence, and functional landscapes across the primate phylogeny. The resulting data sets will enable the connection of genotypes to phenotypes and provide new insight into aspects of the genetics of primate traits, including human diseases. In this Review, we describe the existing genome assemblies as well as genetic variation and functional genomic data sets. We highlight some of the challenges with sample acquisition. Finally, we explore how technological advances in single-cell functional genomics and induced pluripotent stem cell-derived organoids will facilitate our understanding of the molecular foundations of primate biology.

A substantial proportion of disease risk for common complex disorders is attributable to environmental exposures and pollutants. An appreciation of how environmental pollutants act on our cells to produce deleterious health effects has led to advances in our understanding of the molecular mechanisms underlying the pathogenesis of chronic diseases, including cancer and cardiovascular, neurodegenerative and respiratory diseases. Here, we discuss emerging research on the interplay of environmental pollutants with the human genome and epigenome. We review evidence showing the environmental impact on gene expression through epigenetic modifications, including DNA methylation, histone modification and non-coding RNAs. We also highlight recent studies that evaluate recently discovered molecular processes through which the environment can exert its effects, including extracellular vesicles, the epitranscriptome and the mitochondrial genome. Finally, we discuss current challenges when studying the exposome - the cumulative measure of environmental influences over the lifespan - and its integration into future environmental health research.

Inter-individual variability in drug response, be it efficacy or safety, is common and likely to become an increasing problem globally given the growing elderly population requiring treatment. Reasons for this inter-individual variability include genomic factors, an area of study called pharmacogenomics. With genotyping technologies now widely available and decreasing in cost, implementing pharmacogenomics into clinical practice - widely regarded as one of the initial steps in mainstreaming genomic medicine - is currently a focus in many countries worldwide. However, major challenges of implementation lie at the point of delivery into health-care systems, including the modification of current clinical pathways coupled with a massive knowledge gap in pharmacogenomics in the health-care workforce. Pharmacogenomics can also be used in a broader sense for drug discovery and development, with increasing evidence suggesting that genomically defined targets have an increased success rate during clinical development.

Chemical modifications to nucleic acids occur across the kingdoms of life and carry important regulatory information. Reliable high-resolution mapping of these modifications is the foundation of functional and mechanistic studies, and recent methodological advances based on next-generation sequencing and long-read sequencing platforms are critical to achieving this aim. However, mapping technologies may have limitations that sometimes lead to inconsistent results. Some of these limitations are technical in nature and specific to certain types of technology. Here, however, we focus on common (yet not always widely recognized) pitfalls that are shared among frequently used mapping technologies and discuss strategies to help technology developers and users mitigate their effects. Although the emphasis is primarily on DNA modifications, RNA modifications are also discussed.

Macroautophagy and microautophagy are highly conserved eukaryotic cellular processes that degrade cytoplasmic material in lysosomes. Both pathways involve characteristic membrane dynamics regulated by autophagy-related proteins and other molecules, some of which are shared between the two pathways. Over the past few years, the application of new technologies, such as cryo-electron microscopy, coevolution-based structural prediction and in vitro reconstitution, has revealed the functions of individual autophagy gene products, especially in autophagy induction, membrane reorganization and cargo recognition. Concomitantly, mutations in autophagy genes have been linked to human disorders, particularly neurodegenerative diseases, emphasizing the potential pathogenic implications of autophagy defects. Accumulating genome data have also illuminated the evolution of autophagy genes within eukaryotes as well as their transition from possible ancestral elements in prokaryotes.

RNAs are central to fundamental biological processes in all known organisms. The set of possible intramolecular interactions of RNA nucleotides defines the range of alternative structural conformations of a specific RNA that can coexist, and these structures enable functional catalytic properties of RNAs and/or their productive intermolecular interactions with other RNAs or proteins. However, the immense combinatorial space of potential RNA sequences has precluded predictive mapping between RNA sequence and molecular structure and function. Recent advances in high-throughput approaches in vitro have enabled quantitative thermodynamic and kinetic measurements of RNA-RNA and RNA-protein interactions, across hundreds of thousands of sequence variations. In this Review, we explore these techniques, how they can be used to understand RNA function and how they might form the foundations of an accurate model to predict the structure and function of an RNA directly from its nucleotide sequence. The experimental techniques and modelling frameworks discussed here are also highly relevant for the sampling of sequence-structure-function space of DNAs and proteins.