Browse Articles

A collection of articles in Nature describe insights into disease-associated genetic variants obtained from the genetically isolated Finnish population.

Julio Collado-Vides recalls two 2005 publications that provide a conceptual framework based on a statistical thermodynamics approach to quantitatively model the regulatory activity at promoters subject to regulation by multiple transcription factors.

In this Review, the authors discuss our latest understanding of evolutionary genetic changes that are specific to humans, which might endow uniquely human traits and capabilities. They describe how new cellular and molecular approaches are helping to decipher the functional implications of these human-specific changes.

This journal club by Elisa Oricchio highlights two studies published in 2012, which used chromatin conformation capture methods to detect the formation of self-interacting chromatin regions, known as topologically associating domains (TADs).

Magda Bienko highlights a landmark paper by Lieberman-Aiden et al., which in 2009 reported the development of high-throughput chromosome conformation capture (Hi-C), revolutionizing the field of 3D genome biology.

Two studies have revealed that the characteristic distribution of N6-methyladenosine (m⁶A) — an RNA modification known to be functionally important for mRNA metabolism among other processes — in mRNA is shaped by the exon junction complex during splicing.

Environmental pollutants have been shown to disrupt molecular mechanisms underlying common complex diseases. The authors review the interplay of environmental stressors with the human genome and epigenome as well as other molecular processes, such as production of extracellular vesicles, epitranscriptomic changes and mitochondrial changes, through which the environment can exert its effects.

In this Review, Munir Pirmohamed provides an overview of the current state of the pharmacogenomics field, using examples of clinically relevant drug–gene associations, before outlining the steps needed for implementation of pharmacogenomics into clinical practice. The role of pharmacogenomics in drug discovery and development is also considered.

Two new studies in Nature Biotechnology describe cellular recording systems that incorporate time-resolved optical signals into self-assembling protein filaments.

In this Journal club, Meritxell Huch recalls a dogma postulated by Hayflick in 1961, that the capacity for propagating primary epithelial cells with normal ploidy is limited — a theory that persisted until the advent of organoid cultures.

The ability to map DNA and RNA modifications has improved our understanding of these marks, but in some cases inconsistent results have been problematic. Here, Kong et al. discuss how to recognize and resolve issues associated with commonly used sequencing-based approaches to minimize mapping errors.

A study in Nature reports comprehensive, genome-wide mapping of the human methylome that provides mechanistic insights into gene regulation and offers great potential for analysis of cell-free DNA.

Lacaze et al. caution against the use of polygenic scores alone for population screening in the absence of monogenic testing.

Sérgio Pena discusses a 2019 study by Gruhn et al., which showed that meiotic chromosome segregation errors originating in oocytes determine the curve of female fertility in humans.

Selene Fernandez-Valverde recalls a seminal publication by Jacob and Monod to showcase how thoughtful reasoning and extrapolation of limited observations can provide meaningful insights into complex systems.

Macroautophagy and microautophagy involve characteristic membrane dynamics regulated by autophagy-related proteins to degrade cytoplasmic material in lysosomes. In this Review, the authors summarize recent progress in elucidating these highly conserved processes, the pathological relevance of autophagy-related genes in Mendelian and complex diseases, and the evolution of the autophagy pathway.

The vast combinatorial sequence space of RNAs has prohibited quantitative mapping from nucleotide sequence to structure and function. New biochemical methods in vitro, which carry out measurements on hundreds of thousands of molecules at the same time, are now beginning to solve this issue.

In this Review, the authors describe how advances in comparative primate genomics — complemented by multi-layered omic resources and primate cell systems — are providing insights into the evolution of primates and the genetic underpinnings of key traits of developmental and biomedical importance.

Two new studies in Science characterize a CRISPR-associated nuclease–protease system that can be leveraged as a programmable protease-based RNA sensor.

Alternative splicing of pre-mRNAs is key for cellular function and underpins the aetiology of numerous diseases. Here, we review major advances in understanding the structures and functions of the splicing machinery and its regulation, and in harnessing this knowledge for the design of novel therapies.