Genomics research has historically been biased toward individuals of European ancestry, which has the potential to exacerbate health inequities (Martin, A.R. et al.) To reduce these disparities, current efforts in human genetics emphasize the inclusion of diverse populations (All of Us Research Program Investigators). Here, we highlight recent preprints that focus on the intricacies of researching participants with multiple genetic ancestries.

Public interpretations of genetic science in popular media shape its meaning, regulation, and sometimes even its trajectory. Drawing on examples from film and television, we argue that cultural narratives are not merely reflections of science but active forces in the production of genetic meaning.

Mutational robustness, the ensemble of mechanisms that allow organisms to maintain a stable phenotype despite genetic mutations, affects adaptive evolution in several ways. Many models have attempted to explain how mutational robustness might evolve and shape adaptation, but the variety of approaches and assumptions complicates a clear synthesis. Here, we categorize and critically discuss the main approaches for modeling the evolutionary causes and consequences of mutational robustness. We discuss how robustness can emerge from aspects of biological organization (e.g., modularity, critical dynamics) and selection (e.g., stabilizing selection) and how robustness can both enhance and constrain evolvability [e.g., through cryptic genetic variation (CGV)]. We conclude by discussing challenges related to model complexity and computational cost and outline the foremost outstanding questions.

Twenty-five years after the histone code hypothesis proposed that combinations of histone post-translational modifications (PTMs) direct gene regulation, fundamental questions remain unresolved. Here, I outline a call for a multi-laboratory initiative, termed HistENCODE, to systematically decipher functional relationships between histone PTMs via direct mutagenesis of histone N-terminal tail residues.

The DNA mismatch repair (MMR) system is classically viewed as being anti-recombinogenic during meiosis because it mediates heteroduplex rejection to inhibit homeologous recombination, leading to postzygotic isolation between closely related species. In this forum article, conversely, we summarize a very recent study showing that homologous recombination (HR) proteins can antagonize MMR.

Despite ongoing efforts, no African country is on track to achieve its agricultural transformation goals, as based on the 2014 Malabo Declaration's objective of accelerated agricultural growth and transformation. How can we ensure that locally relevant scientific innovations are adopted? Without co-creation, inclusion, and ethical delivery, science fails to take root socially.

Researchers often assume genomic results are too complex for lay communities, but heredity concepts are widely understood. Effective return of results depends on cultural context, clear communication, and collaboration with communities. Tailored, respectful approaches foster trust and ensure research benefits are meaningful, accessible, and empowering.

Visual representations are indispensable in genetics education; yet, their apparent simplicity can mask deep conceptual challenges for learners. We summarize empirical evidence for this 'illusion of clarity' and describe resources that may help genetic instructors dispel this illusion.

Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We review recent advances in transcription-associated DNA breaks and their role as an essential player in endogenous fragility. We highlight the contrast between replication-dependent transcriptional breaks (e.g., transcription-replication conflicts) and replication-independent transcriptional breaks (resulting from transcription itself). We outline two types of transcriptional double-strand breaks (DSBs): promoter-associated breaks that are linked to gene activation, and gene-body breaks that occur stochastically from transcription byproducts. We discuss how supercoiling, R-loops, and enhancer-promoter looping at super-enhancer (SE)-regulated loci can increase DNA fragility and thereby create a distinct Achilles' heel, and propose that targeting the coupling between SE-driven transcription and DNA repair could offer new therapeutic strategies for cancer.

Complex diseases are heterogeneous and evolve along a continuum, limiting individual-level prediction with current approaches. The Human Phenotype Project (HPP) integrates deep phenotyping with generative artificial intelligence (AI) to identify early deviations in health parameters. While the project has already provided significant insights, the challenge is converting these findings into actionable, equitable, and scalable interventions, advancing precision healthcare across diverse populations.

Transcriptional cis-regulation has emerged as the predominant force underlying the evolution of phenotypic diversity, yet our understanding of it is still rudimentary. While empirical comparative genomic approaches have been quite informative, they also suffer from numerous confounders and limited scalability. Here we propose using machine-learning-based methods that predict cis-regulatory activity from DNA sequence to perform in silico 'genome transplants' to predict cis-regulatory features as if the genome from one species had been transplanted into the nuclei of another species. Inference of natural selection from the resulting genome-wide catalogs of cis-regulatory divergence could be far more powerful, efficient, and widely applicable than current empirical approaches, enabling unprecedented insights into the genetic basis of biodiversity across the tree of life.

The power of short-read DNA sequencing in biodiversity research and evolutionary genomics is rapidly growing due to advances in technology and bioinformatics. Short-read sequencing offers powerful solutions for taxonomic identification, biomass estimation, and phylogenetic reconstruction. Moreover, short-read data enable robust estimation of genome size and repeat content, offering valuable insights into genome evolution. Though growing in popularity, long-read genome assemblies are often not feasible with material from museum collections or raw biodiversity samples. With the growing demand for DNA-based approaches in biodiversity research, short-read genomics provides an easily generated universal data source spanning all levels from individual genomes to ecosystems, and including all species on Earth, to achieve the objectives of the Global Biodiversity Framework (GBF) for the preservation of biodiversity.

Gene activity is intricately shaped by its chromatin environment. Deciphering the chromatin landscape is essential for understanding the complex regulatory networks governing gene function. The newly re-recognized DNA N-methyladenine (6mA) is relatively scarce in multicellular eukaryotes, which has facilitated the development of innovative chromatin profiling approaches employing sequence-independent 6mA methyltransferases (MTases) to introduce exogenous 6mA. In this review, we summarize recent advances in leveraging exogenous 6mA deposition and long-read sequencing in three major applications: chromatin landscape profiling, protein-DNA interaction mapping, and targeted epigenetic editing. For each, we outline representative workflows, highlight technical advantages, and discuss current challenges and prospects for optimization. Together, this review underscores the emerging power of exogenous 6mA as a versatile tool for decoding chromatin architecture and gene regulation.

Recent studies have reported that catalytically dead histone-modifying enzymes can rescue the function of their null alleles. Histone 'replacement' experiments have similarly found a lack of phenotypes for some modifications. Do these findings foretell a paradigm shift for the histone code hypothesis? Here, we discuss these results through the lens of ecology, evolution, and development ('eco-evo-devo') to provide context. We then highlight recent 'top-down' approaches, which start from environmentally influenced phenotypes and then attempt to identify causal mechanisms; placing function before molecule. Using this strategy, recent work in invertebrates has found key roles for histone acetylation and small RNAs in developmental plasticity. The synthesis of traditional 'bottom-up' with new 'top-down' approaches can resolve which molecules are epiphenomenal and which are truly epigenetic.

De-extinction critiques focus on animal welfare, ecosystem disruption, threats to traditional conservation, and anxiety about human hubris. Respondents argue that humanity is obligated to reverse damage to species (natural or human-caused) and to pursue the benefits for conservation science and human health generated by the research.

Synthetic DNA technologies may eventually enable the creation of synthetic gametes, which would offer precise control over genetic inheritance. This possibility raises profound ethical questions about human identity, genetic selection, and evolutionary boundaries. While synthetic gametes sidestep person-affecting ethical concerns, they present challenges for balancing reproductive autonomy and minimizing heritable disease, prompting interdisciplinary reflection.

Symbiosis is a fundamental characteristic of eukaryotic biology. Arthropods, including insects, often harbor maternally inherited endosymbiotic microbes, some of which have evolved the ability to selectively kill male hosts - a phenomenon known as 'male killing.' The evolutionary history and mechanisms of symbiont-induced male killing have remained poorly understood. However, recent studies have revealed a remarkable diversity of male-killing strategies and their associated causative genes in diverse bacteria and viruses that target different aspects of the host reproductive system. Some insects have evolved various suppressor genes to counteract male-killing actions. This review synthesizes the current knowledge on the evolution and mechanisms underlying microbe-induced male killing and explores their broader implications for the ecology and evolution of eukaryotic life forms.

Transposable elements (TEs) - long considered 'junk DNA' - challenge the binary of threat and therapeutic opportunity in cancer. Their reactivation is not a singular event but a convergence of evolutionary legacy, regulatory disruption, and technological insight. This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state. Across regulatory control, viral mimicry, protein-coding potential, and antigen presentation, TEs blur the line between harm and utility. Each example reflects a broader theme: context defines consequence. By tracing historical shifts and technological advances, we argue for an integrated view: one where TEs are not just anomalies, but dynamic agents in the complexity of cancer.