Jun 2025

• Advisory Board and Contents

  Science & Society

  • 

    Genetic databases in the era of ‘DSI’ benefit-sharing

    • Mathieu Rouard,
    • Amber Hartman Scholz,
    • Michael Halewood

    Open Access

    Genetic databases drive research by enabling open access. Recently, parties to the Convention on Biological Diversity agreed on new rules for sharing benefits from the use of digital sequence information (DSI) which upholds open access, and also imposed new requirements for data depositors, database managers, and users.

Spotlights

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  DNA lesions piece together impossible trees

  • Claudia Arnedo-Pac,
  • Sarah J. Aitken

  Open Access

  DNA lesions can persist through multiple cell cycles, resulting in mutational strand asymmetry, multiallelic variation, and somatic mosaicism. But for how long do these lesions persist? Recent work from Spencer Chapman et al. shows that they can last for months to years, even arising from endogenous exposures in utero.
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  The impact of human accelerated regions on neuronal development

  • Jose Manuel Ruiz-Jiménez,
  • Gabriel Santpere

  Open Access

  Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome since the divergence from chimpanzees. Some of these regions are suspected to have contributed to the evolution of unique human brain features. Recently, Cui et al. conducted a large-scale study identifying which HARs may have influenced neuronal function.

Opinions

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  The Genomic Code: the genome instantiates a generative model of the organism

  • Kevin J. Mitchell,
  • Nick Cheney

  Open Access

  How does the genome encode the form of the organism? What is the nature of this genomic code? Inspired by recent work in machine learning and neuroscience, we propose that the genome encodes a generative model of the organism. In this scheme, by analogy with variational autoencoders (VAEs), the genome comprises a connectionist network, embodying a compressed space of ‘latent variables’, with weights that get encoded by the learning algorithm of evolution and decoded through the processes of development. The generative model analogy accounts for the complex, distributed genetic architecture of most traits and the emergent robustness and evolvability of developmental processes, while also offering a conception that lends itself to formalization.
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  What does evolution make? Learning in living lineages and machines

  • Benedikt Hartl,
  • Michael Levin

  How does genomic information unfold, to give rise to self-constructing living organisms with problem-solving capacities at all levels of organization? We review recent progress that unifies work in developmental genetics and machine learning (ML) to understand mapping of genes to traits. We emphasize the deep symmetries between evolution and learning, which cast the genome as instantiating a generative model. The layer of physiological computations between genotype and phenotype provides a powerful degree of plasticity and robustness, not merely complexity and indirect mapping, which strongly impacts individual and evolutionary-scale dynamics. Ideas from ML and neuroscience now provide a versatile, quantitative formalism for understanding what evolution learns and how developmental and regenerative morphogenesis interpret the deep lessons of the past to solve new problems. This emerging understanding of the informational architecture of living material is poised to impact not only genetics and evolutionary developmental biology but also regenerative medicine and synthetic morphoengineering.

Reviews

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  Genetics of human handedness: microtubules and beyond

  • Sebastian Ocklenburg,
  • Annakarina Mundorf,
  • Jutta Peterburs,
  • Silvia Paracchini

  Open Access

  Handedness (i.e., the preference to use either the left or the right hand for fine motor tasks) is a widely investigated trait. Handedness heritability is consistently estimated to be 25%. After decades of research, recent large-scale genome-wide association and exome sequencing studies have identified multiple genes associated with handedness and highlighted tubulin genes. Tubulin genes play a role in several processes during brain development that may be relevant for handedness ontogenesis, including axon guidance, axon growth, and forming the inner structure of motile cilia. Moreover, tubulin genes are associated with several psychiatric disorders. This finding therefore may offer insights into biological pathways mediating the link between handedness, brain asymmetries, and psychiatric traits.
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  The ABCs of the H2Bs: The histone H2B sequences, variants, and modifications

  • Anna J. Voss,
  • Erica Korb

  Histone proteins are the building blocks of chromatin, and function by wrapping DNA into complex structures that control gene expression. Histone proteins are regulated by post-translational modifications (PTMs) and by histone variant exchange. In this review, we will provide an overview of one of these histones: H2B. We will first define the sequences of human and mouse H2B proteins and discuss potential designations for canonical H2B. We will also describe the differential functions of H2B variants compared with canonical H2B. Finally, we will summarize known H2B modifications and their functions in regulating transcription. Through review of H2B genes, proteins, variants, and modifications, we aim to highlight the importance of H2B for epigenetic and transcriptional regulation of the cell.
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  Revealing microRNA regulation in single cells

  • Ranjan K. Maji,
  • Matthias S. Leisegang,
  • Reinier A. Boon,
  • Marcel H. Schulz

  Open Access

  MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation. Single-cell RNA-sequencing (scsRNA-seq) technologies, together with computational strategies, enable exploration of miRNAs, isomiRs, and interacting RNAs at the cellular level. By integration with other miRNA-associated single-cell modalities, miRNA roles can be resolved at different stages of processing and regulation. In this review we discuss (i) single-cell experimental assays that measure miRNA and isomiR abundances, and (ii) computational methods for their analysis to investigate the mechanisms of miRNA biogenesis and post-transcriptional regulation.
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  Unraveling the genetics of underwater caddisfly silk

  • Samantha Standring,
  • Jacqueline Heckenhauer,
  • Russell J. Stewart,
  • Paul B. Frandsen

  Open Access

  Hundreds of thousands of arthropod species use silk to capture prey, build protective structures, or anchor eggs. While most silk-producers are terrestrial, caddisflies construct silken capture nets and portable cases in aquatic environments. Given the potential practical applications of this underwater bioadhesive, there is an emerging body of research focused on understanding the evolution of the genetic architecture of aquatic silk. This research has unveiled molecular adaptations specific to caddisfly silk, such as extensive phosphorylation of the primary silk protein and the existence of numerous unique accessory silk proteins. We discuss the molecular evolution of caddisfly silk genes, how they interact with the environment, and suggest future directions for caddisfly silk genetics research.

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