Aug 2025

• Advisory Board and Contents

Science & Society

• Genomic newborn screening: exploring opportunities and navigating pitfalls while ensuring inclusivity

  • Alban Ziegler,
  • Wendy K. Chung

  Advances in genome sequencing (GS) have led to consented research evaluating DNA sequencing as a first-tier screening tool to expand the conditions included in newborn screening (NBS). Those pilot studies are confirming its feasibility but also delineate challenges to be solved. Preliminary results are guiding the design of infrastructure to address these challenges.

Spotlights

• Mendel elucidated: Big Science comes to the humble garden pea

  • Norman F. Weeden

  News flash: in a recent article by Feng et al., one of Mendel ‘factors’ is shown not to result in the expected 3:1 segregation ratio, and about half of the traits he investigated are produced by large insertions or deletions. Do genetic textbooks need to be revised?
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  Selfish B chromosome evades genome elimination

  • Cécile Courret

  The mealybug B chromosome evades paternal genome elimination (PGE) by mimicking maternal chromatin states, ensuring its transmission. Vea et al. conducted a detailed genomic and transcriptomic analysis, highlighting a histone acetyltransferase potentially driving this behavior. Their findings illuminate selfish chromosome strategies and epigenetic manipulation of inheritance systems.
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  Psychiatric disorders: teasing apart genetic similarities and differences

  • Jiayi Xu,
  • Laura M. Huckins

  Given the high comorbidity between psychiatric disorders, previous studies have focused on genetic factors shared across the disorders. In a recent preprint, Grotzinger et al. comprehensively investigated shared and disorder-specific genetic factors across 14 neuropsychiatric disorders. Here, we discuss how this investigation could improve psychiatric nosology and therapeutic development.

Forum

• Advancing GWAS of human communication

  • Rosa S. Gisladottir

  Open Access

  The last decade has seen an explosion in genome-wide association studies (GWAS) on almost any imaginable phenotype. Unfortunately, humanity’s most distinctive trait – communication, broadly construed – has been underserved. In this forum article I review recent advances and promising avenues that may help us understand the genetics and evolution of human communication.

Reviews

• Featured Article
  

  Molecular circuits for genomic recording of cellular events

  • Wei Chen,
  • Junhong Choi

  Advances in precise genome editing are enabling genomic recordings of cellular events. Since the initial demonstration of CRISPR-based genome editing, the field of genomic recording has witnessed key strides in lineage recording, where clonal lineage relationships among cells are indirectly recorded as synthetic mutations. However, methods for directly recording and reconstructing past cellular events are still limited, and their potential for revealing new insights into cell fate decisions has yet to be realized. The field needs new sensing modules and genetic circuit architectures that faithfully encode past cellular states into genomic DNA recordings to achieve such goals. Here we review recently developed strategies to construct diverse sensors and explore how emerging synthetic biology tools may help to build molecular circuits for genomic recording of diverse cellular events.
• Featured Article
  

  Unlocking the potential of CRISPR-associated transposons: from structural to functional insights

  • Francisco Tenjo-Castaño,
  • Sweta Suman Rout,
  • Sanjay Dey,
  • Guillermo Montoya

  Clustered regularly interspaced short palindromic repeats (CRISPR)-associated transposons (CASTs) are emerging genome-editing tools that enable RNA-guided DNA integration without inducing double-strand breaks (DSBs). Unlike CRISPR-associated (Cas) nucleases, CASTs use transposon machinery to insert large DNA segments with high precision, potentially reducing off-target effects and bypassing DNA damage responses. CASTs are categorized into classes 1 and 2, each employing distinct mechanisms for DNA targeting and integration. Recent structural insights have elucidated how CASTs recognize target sites, recruit transposases, and mediate insertion. These advances position CASTs as promising tools for genome engineering in bacteria and possibly in mammalian cells. Key challenges remain in enhancing efficiency and specificity, particularly for therapeutic use. Ongoing research aims to evolve CAST systems for precise, large-scale genome editing in human cells.
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  Strategies for studying sex differences in brain aging

  • Victor A. Ansere,
  • Seung-Soo Kim,
  • Francesca Marino,
  • Katherine Morillo,
  • Dena B. Dubal,
  • Coleen T. Murphy,
  • Yousin Suh,
  • Bérénice A. Benayoun

  Open Access

  Studying sex effects and their underlying mechanisms is of major relevance to understanding brain health. Despite growing interests, experimentally studying sex differences, particularly in the context of aging, remains challenging. Since sex chromosomal content influences gonadal development, separating the effects of gonadal hormones and chromosomal factors requires specific model systems. Here, we highlight rodent and tractable models for examining sex dimorphism in brain and cognitive aging. In addition, we discuss multi-omic and bioinformatic approaches that yield biological insights from animal and human studies. This review provides a comprehensive overview of the diverse toolkit now available to advance our understanding of sex differences in brain aging.
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  Epitranscriptome–epigenome interactions in development and disease mechanisms

  • Chengyu Li,
  • Kexuan Chen,
  • Xiaoyu Li,
  • Xushen Xiong

  Crosstalk between epitranscriptomic modifications to RNA and epigenomic modifications to DNA and histones plays fundamental roles in development and disease. Here, we summarize two major regulatory modes of the crosstalk between the epigenome and epitranscriptome. In the ‘cis mode’, the crosstalk occurs co-transcriptionally, with direct interactions observed between epigenetic modifications mediated by their regulators. In the ‘trans mode’, the modification of an epigenetic layer regulates the expression of another epigenetic layer’s writers/erasers and subsequently induces downstream epigenetic alteration. Additionally, we focus on the functional roles of the crosstalk mechanism in physiological and pathological contexts, including development, differentiation, cancer, and complex genetic diseases. Lastly, we discuss the potential future directions for a systematic understanding of epigenetic crosstalk in development and disease.
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  New dimensions in the molecular genetics of insect chemoreception

  • Gaëlle J.S. Talross,
  • John R. Carlson

  Chemoreception is the foundation of olfaction and taste, which in insects underlie the detection of humans to whom they spread disease and crops that they ravage. Recent advances have provided clear and in some cases surprising new insights into the molecular genetics of chemoreception. We describe mechanisms that govern the choice of a single Odorant receptor gene by an olfactory receptor neuron in Drosophila. We highlight genetic and epigenetic mechanisms by which chemoreceptor expression can be modulated. Exitrons, RNA editing, and pseudo-pseudogenes in chemosensory systems are described. We summarize key insights from the recent structural determinations of odorant and taste receptors. Finally, new molecular components of chemosensory systems, including long noncoding RNAs, are described.
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  Polyploidy in potatoes: challenges and possibilities for climate resilience

  • Helen H. Tai,
  • Laura M. Shannon,
  • Martina V. Strömvik

  Open Access

  Solanum section Petota Dumort. consists of tuber-bearing species (i.e., the cultivated potatoes and their wild relatives) that have both asexual and sexual propagation, variation in ploidy, and reproductive isolation. These species have undergone adaptation to a diversity of climates, altitudes, photoperiods, and geographical range. The section defies characterization with the biological species concept due to interspecies hybridization, allo- and auto-polyploidy, and phenotypic plasticity. Genetic studies, and more recently genome sequencing and pangenome analyses, are fostering a greater understanding of genetic processes that shape genome evolution and speciation in the section, shedding light on the phylogeny and providing insights on utilization of potato crop wild relatives in breeding for climate-resilient potato varieties.

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