Annual review of genetics最新文献

Specialized metabolism plays a central role in mediating ecological interactions and adaptive responses in plants, while leaving enduring signatures in genome structure and evolution. Here, we synthesize advances in genomics, biochemistry, and evolutionary biology into a metabolite-driven genetic diversification (MGD) framework, in which metabolite chemistry biases the generation, retention, and reuse of genetic variation. When metabolic flux produces reactive, inhibitory, or otherwise costly intermediates, pathways handling these liabilities recurrently recruit gene dosage changes, duplication, and divergence at catalytic and regulatory choke points. These biases do not impose deterministic outcomes; instead, they shape which genomic variants are preferentially sampled and retained under selection, giving rise to predictable patterns of genomic change. Genome multiplication-through whole-genome duplication, allopolyploidy, and cell type-specific endoreduplication-amplifies these effects by altering dosage balance, regulatory context, and retention trajectories. Integrating MGD with genome-scale dosage dynamics explains why specialized metabolism repeatedly converges on similar solutions across plant lineages, even amid extensive genomic turnover and chemical diversity.

As a fundamental biological principle, genomic information is typically transmitted vertically from parent to offspring. Occasionally, however, genetic material is transferred horizontally between species. Transposable elements (TEs) are frequently involved in such horizontal transfer (HT), possibly due to their ability to move in genomes. HT has been particularly well-studied in Drosophila melanogaster, a key model organism for evolutionary and ecological research. Recent studies have revealed that HT triggered the invasion of 12 different TEs in the D. melanogaster genome over the past 200 years. This finding challenges our traditional view of genome evolution, suggesting that TE invasions may not only be isolated events that can be ignored as rare exceptions but could represent recurrent events that continuously reshape genomes. In this review, we trace the history of how these 12 invasions were discovered and outline the lines of evidence supporting them. We also discuss the potential evolutionary consequences of these TE invasions, including their roles in adaptation, genome evolution, speciation, and extinction risk. Finally, we highlight open questions and directions for future research. In particular, it will be essential to test whether other organisms also exhibit similarly high rates of recent TE invasions and to assess whether human activity triggered the high rate of invasions.

For over a century, biologists have used test tubes and petri dishes to investigate life. By studying bacteria in laboratory conditions, generations of scientists have amassed a wealth of biological knowledge. However, simple experimental systems remove complexity, leading us to question how our knowledge translates to the natural world. Approaches combining microfluidics and molecular biology have made rapid progress, filling this gap by reintroducing experimental complexity. In our review, we highlight how microfluidics has shifted and enhanced our understanding of several core molecular microbiology processes. In Section 1, we follow the journey of bacterial cells as they colonize surfaces, emphasizing that this is not a linear process. In Section 2, we explore how the interplay of physical, chemical, and biological features impacts surface-attached communities. Along the way, we highlight how using microfluidics captures bacterial behavior that classical approaches overlook, often revealing unexpected and counterintuitive outcomes.

Multicellularity necessitated the evolution of cellular diversity and specialization, yet across organisms, the retention of cellular plasticity within defined physiological contexts is a recurring principle. Here, we examine early-diverging metazoans to reevaluate the evolutionary logic of stemness. Rather than viewing stem cells as exceptional, we argue that cellular plasticity represents a deeply conserved attribute of early life. The ability of cells to remain responsive, multipotent, and regenerative under ecological or physiological contexts challenges the notion of cellular identity. We integrate evidence across three layers: evolutionary origins of cellular plasticity, systemic physiological axes that govern stem cell behavior, and metabolic and epigenetic mechanisms that execute fate decisions. This synthesis reveals that stemness is not a default cellular state but a licensed state, permitted when organism-level physiological signals align with local tissue demands. Within this framework, regeneration, age-associated decline, and cancer emerge as evidence of how effectively systemic governance regulates cellular plasticity across multicellular life.

Dicer has long been viewed as the RNAse III enzyme that generates small regulatory RNAs to drive RNA interference (RNAi) machinery and posttranscriptional gene silencing. However, a growing body of evidence reveals that Dicer's functional landscape extends far beyond its canonical role in the cytoplasmic RNAi pathway. In this review, we delineate the classical, RNAse III-dependent small RNA processing activities from an expanding set of noncanonical functions in which Dicer operates independently of RNAi outputs. We highlight emerging principles that underlie these functions, including structural and regulatory principles, with a focus on nuclear functions, posttranslational regulation, and noncanonical substrates. We then explore how Dicer intersects with genome integrity pathways, transcriptional programs, and cellular response to DNA damage. Finally, we propose an integrated conceptual framework in which Dicer acts as a multifunctional regulator of chromatin architecture and genome stability, as we consider how perturbations of these pathways contribute to disease.

Meiosis is a specialized cell division essential for sexual reproduction, generating haploid gametes through two consecutive nuclear divisions following a single round of DNA replication. During an extended meiotic prophase I, chromosomes undergo elaborate rearrangements, such as pairing, synapsis, and recombination, culminating in crossovers that physically link homologs for accurate segregation. Errors in these processes cause aneuploidy, a leading contributor to infertility, miscarriage, and congenital disorders. These chromosomal events must be precisely coordinated with cell cycle transitions through signaling pathways involving cell cycle and DNA damage checkpoint kinases, as well as ubiquitin-mediated regulation. These pathways control the timing and levels of programmed DNA double-strand breaks, monitor synapsis and crossover formation, and enforce surveillance checkpoints that eliminate defective cells. This review examines how signaling networks orchestrate chromosome dynamics during meiotic prophase, highlighting conserved principles and organism-specific adaptations that ensure faithful genetic transmission across generations.

Transposable elements (TEs), originally characterized in maize, are ubiquitous features of eukaryotes and replicate within genomes independent of the host replication cycle. This replicative advantage can result in genomes that are almost entirely composed of these selfish genetic elements. Most mutations caused by TE insertions are harmful, and all eukaryotes have evolved mechanisms to limit TE replication. This process requires the careful distinction between self and nonself, or host versus TE. Eukaryotic genome defense commonly relies on Argonaute proteins that block the TE replication cycle, guided by small RNAs that detect harmful TE transcripts. Because no system of immunity is perfect, genes can be caught in the crossfire and inappropriately silenced. Here, mainly focusing on maize and Drosophila, we discuss how off-target small RNA silencing can arise. This genomic immunity can shape TE evolutionary dynamics, establish novel modes of adaptation and epigenetic inheritance, and establish evolutionary feedback that shapes the evolution of gene silencing itself.

Domesticated gag genes derived from long terminal repeat (LTR) retrotransposons are widespread in mammals and occur in other metazoans, including Drosophila and zebrafish. Their protein products commonly contain a capsid (CA) domain, and many retain the ability to assemble capsid-like particles that package RNA, and potentially other biomolecules, with emerging roles in intercellular communication, neuronal signaling, placental gene regulation, and fertility. Biochemical, genetic, and structural studies have identified the core domains that are necessary and sufficient for capsid formation, even in the absence of accessory proteins. Several systems also exhibit selective self-RNA packaging directed by cis elements, suggesting rules that could be harnessed for programmable cargo selection. Building on this foundation, recent efforts have developed host-encoded Gag CA proteins for delivery applications, ranging from engineered systems to approaches that exploit naturally preloaded capsids. In addition to established platforms such as adeno-associated viruses (AAVs), lipid nanoparticles (LNPs), and nonintegrating lentiviral systems, domesticated Gag CA proteins may offer complementary features such as lower immunogenicity, flexible cargo capacity, and tissue-specific targeting. Open questions remain regarding release and cellular entry mechanisms, in vivo tropism, determinants of immunogenicity across family members, and safety.

Centromeres are chromosomal loci required for accurate chromosome segregation in cell division and are defined epigenetically by the centromere-specific histone H3 variant CENP-A. The assembly and maintenance of CENP-A in each cell cycle are critical for continued centromere identity and function. In the germline, centromere identity must be maintained throughout many specialized divisions and preserved in gametes to ensure transgenerational inheritance. The male germline poses a particular challenge for maintaining centromere identity because most histones are removed from sperm chromatin and replaced by protamines in most animal species, causing a potential identity crisis. Here, we discuss the timing and mechanisms of centromere assembly and maintenance throughout spermatogenesis and the impacts on fertility and offspring development. We focus on Drosophila melanogaster, which has served as an informative model of the male germline, but also draw comparisons with other species, highlighting any conservation or adaptations. Finally, we outline unanswered questions in the field, identify technical barriers, and propose potential solutions.

Genetic variation is a major cause of disease susceptibility, and sequence variants can change both protein function and stoichiometry. Though posttranscriptional regulation is a major component of mammalian gene expression control, single-nucleotide polymorphisms (SNPs) within 3' untranslated regions (UTRs) remain an underexplored source of variation impacting human health. Nevertheless, seminal studies have found that functionally relevant SNPs, including expression quantitative trait loci (eQTLs), are enriched in 3'UTRs. These discoveries highlight the importance of SNPs within 3'UTRs. Here, we provide an overview of techniques used to prioritize and validate 3'UTR SNPs. Computational methods, such as association assays and scoring frameworks, allow for SNP prioritization, and recent experimental methods have enabled the validation of many SNPs in parallel. We discuss examples of 3'UTR SNPs that are relevant to human health and development, as well as how the patterns and prevalence of 3'UTR SNPs can be used to identify selection on the cis-regulatory sites and trans-factors that underlie posttranscriptional regulation.