May 2025

Volume 41Issue 5p359-450, e1-e2
Transposable elements (TEs) can "jump" through the genome, much like monkeys move through a forest. But various host defense mechanisms actively counteract their transposition. In this issue, Yuka Iwasaki, Keisuke Shoji, Shinichi Nakagawa, Tomoichiro Miyoshi, and Yukihide Tomari discuss these host defense mechanisms and explore the dynamic coevolution of TEs and host defenses in animals. They highlight how these defense mechanisms not only safeguard host genomes but also drive genetic innovation, constantly reshaping genome architecture and function. Illustration by Hiroko Uchida....
Transposable elements (TEs) can "jump" through the genome, much like monkeys move through a forest. But various host defense mechanisms actively counteract their transposition. In this issue, Yuka Iwasaki, Keisuke Shoji, Shinichi Nakagawa, Tomoichiro Miyoshi, and Yukihide Tomari discuss these host defense mechanisms and explore the dynamic coevolution of TEs and host defenses in animals. They highlight how these defense mechanisms not only safeguard host genomes but also drive genetic innovation, constantly reshaping genome architecture and function. Illustration by Hiroko Uchida.

Spotlights

  • An innovation in host responses to escalating genomic conflicts

    • Emiliano Martí,
    • Amanda M. Larracuente
    Conflicts between selfish elements and their hosts can trigger rapid structural and regulatory changes in genomes. Chen et al. discovered a novel species-specific innovation in response to a meiotic driver in Drosophila melanogaster. Their discovery highlights a new dimension in adaptive responses to selfish elements, with broad evolutionary consequences.
  • Conserved dynamics of natal down-to-juvenile feather transition

    • Marie Manceau
    Despite the ecological importance of the feather cover during early avian life, the events controlling the transition from natal down to juvenile feathers are poorly understood. Chen et al. demonstrate that this transition is characterized by a series of morphological and molecular changes strikingly conserved between precocial and altricial species.

Forum

  • Empowering continuous evolution of proteins by in vivo mutagenesis

    • Zhanzhi Liu,
    • Jing Wu
    In vivo mutagenesis enriches genetic polymorphism within cells, which is pivotal for triggering continuous evolution. Remarkable strides have been made in this field. Here, we summarize the current in vivo mutagenesis methods focusing on the theme of mutation range and provide an outlook on their future directions, offering inspiration to relevant researchers.

Feature Review

  • Transposon–host arms race: a saga of genome evolution

    • Yuka W. Iwasaki,
    • Keisuke Shoji,
    • Shinichi Nakagwa,
    • Tomoichiro Miyoshi,
    • Yukihide Tomari
    Once considered ‘junk DNA,’ transposons or transposable elements (TEs) are now recognized as key drivers of genome evolution, contributing to genetic diversity, gene regulation, and species diversification. However, their ability to move within the genome poses a potential threat to genome integrity, promoting the evolution of robust host defense systems such as Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KRAB-ZFPs), the human silencing hub (HUSH) complex, 4.5SH RNAs, and PIWI-interacting RNAs (piRNAs). This ongoing evolutionary arms race between TEs and host defenses continuously reshapes genome architecture and function. This review outlines various host defense mechanisms and explores the dynamic coevolution of TEs and host defenses in animals, highlighting how the defense mechanisms not only safeguard the host genomes but also drive genetic innovation through the arms race.

Reviews

  • Evolution of piRNA-guided defense against transposable elements

    • Shashank Pritam,
    • Sarah Signor
    Transposable elements (TEs) shape every aspect of genome biology, influencing genome stability, size, and organismal fitness. Following the 2007 discovery of the piRNA defense system, researchers have made numerous findings about organisms’ defenses against these genomic invaders. TEs are suppressed by a ‘genomic immune system’, where TE insertions within specialized regions called PIWI-interacting RNA (piRNA) clusters produce small RNAs responsible for their suppression. The evolution of piRNA clusters and the piRNA system is only now being understood, largely because most research has been conducted in developmental biology labs using only one to two genotypes of Drosophila melanogaster. While piRNAs themselves were identified simultaneously in various organisms (flies, mice, rats, and zebrafish) in 2006–2007, detailed work on piRNA clusters has only recently expanded beyond D. melanogaster. By studying piRNA cluster evolution in various organisms from an evolutionary perspective, we are beginning to understand more about TE suppression mechanisms and organism–TE coevolution.
  • Emerging insights into the genetics and evolution of human same-sex sexual behavior

    • Thomas Felesina,
    • Brendan P. Zietsch
    Thanks to twin studies, it has been known for decades that human same-sex sexual behavior (SSB) has a substantial heritable component. However, only recently have large genome-wide association studies (GWAS) begun to illuminate the complex genetics involved. These studies have established that SSB is influenced by many common genetic variants, each with tiny but cumulative effects. The evolutionary explanation for the persistence of genetic variants associated with SSB, despite their apparent fitness costs, remains uncertain. In this review, we synthesize advances in understanding the genetic and evolutionary bases of SSB, while identifying the many areas in which we still have much to learn.
  • Chromatin-centric insights into DNA replication

    • Yang Liu,
    • Zhengrong Zhangding,
    • Xuhao Liu,
    • Jiazhi Hu
    DNA replication ensures the precise transmission of genetic information from parent to daughter cells. In eukaryotes, this process involves the replication of every base pair within a highly complex chromatin environment, encompassing multiple levels of chromatin structure and various chromatin metabolic processes. Recent evidence has demonstrated that DNA replication is strictly regulated in both temporal and spatial dimensions by factors such as 3D genome structure and transcription, which is crucial for maintaining genomic stability in each cell cycle. In this review, we discuss the diverse mechanisms that govern eukaryotic DNA replication, emphasizing the roles of chromatin architecture and transcriptional activity within the mammalian chromatin landscape. These insights provide a foundation for future investigations in this field.
  • Transcription and epigenetic factor dynamics in neuronal activity-dependent gene regulation

    • Noriyuki Sugo,
    • Yuri Atsumi,
    • Nobuhiko Yamamoto
    Open Access
    Neuronal activity, including sensory-evoked and spontaneous firing, regulates the expression of a subset of genes known as activity-dependent genes. A key issue in this process is the activation and accumulation of transcription factors (TFs), which bind to cis-elements at specific enhancers and promoters, ultimately driving RNA synthesis through transcription machinery. Epigenetic factors such as histone modifiers also play a crucial role in facilitating the specific binding of TFs. Recent evidence from epigenome analyses and imaging studies have revealed intriguing mechanisms: the default chromatin structure at activity-dependent genes is formed independently of neuronal activity, while neuronal activity modulates spatiotemporal dynamics of TFs and their interactions with epigenetic factors (EFs). In this article we review new insights into activity-dependent gene regulation that affects brain development and plasticity.
  • DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders

    • Chiara Fiorenzani,
    • Adele Mossa,
    • Silvia De Rubeis
    The DEAD/DEAH-box family of RNA helicases (RHs) is among the most abundant and conserved in eukaryotes. These proteins catalyze the remodeling of RNAs to regulate their splicing, stability, localization, and translation. Rare genetic variants in DEAD/DEAH-box proteins have recently emerged as being associated with neurodevelopmental disorders (NDDs). Analyses in cellular and animal models have uncovered fundamental roles for these proteins during brain development. We discuss the genetic and functional evidence that implicates DEAD/DEAH-box proteins in brain development and NDDs, with a focus on how structural insights from paralogous genes can be leveraged to advance our understanding of the pathogenic mechanisms at play.
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