Trends in Genetics最新文献

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.

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.

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.

Recent developments in low-input genomics techniques have greatly advanced the analysis of the order in which DNA is replicated in the genome - that is, replication timing (RT) - and its interrelationships with other processes. RT correlates or anticorrelates with genomic-specific parameters such as gene expression, chromatin accessibility, histone modifications, and the 3D structure of the genome, but the significance of how they influence each other and how they relate to biological processes remains unclear. In this review I discuss the results of recent analyses of RT, the time at which it is remodeled and consolidated during embryogenesis, how it influences development and differentiation, and the regulatory mechanisms and factors involved.

Translation is an ancient molecular information processing system found in all living organisms. Over the past decade, significant progress has been made in uncovering the origins of early translation. Yet, the evolution of translation factors - key regulators of protein synthesis - remains poorly understood. This review synthesizes recent findings on translation factors, highlighting their structural diversity, evolutionary history, and organism-specific adaptations across the tree of life. We examine conserved translation factors, their coevolution, and their roles in different steps in translation: initiation, elongation, and termination. The early evolution of translation factors serves as a natural link between modern genetics and the origins of life. Traditionally rooted in chemistry and geology, incorporating evolutionary molecular biology into the studies of life's emergence provides a complementary perspective on this complex question.

Plant evolutionary research has made leaps in exploring the deep evolutionary roots of embryophytes. A solid phylogenomic framework was established, allowing evolutionary inferences. Comparative genomic approaches revealed that many genes coding for transcription factors, morphogenetic regulators, specialized metabolic enzymes, phytohormone signaling, and more are not innovations of land plants but have a deep streptophyte algal ancestry. Are these just spurious homologs, or do they actualize traits we deem important in embryophytes? Building on streptophyte algae genome data, current endeavors delve into the functional significance of whole cohorts of homologs by leveraging the power of comparative high-throughput approaches. This ushered in the identification of recurrent themes in function, ultimately providing a functional genomic definition for the toolkit of plant terrestrialization.

Genomic data can be used to reconstruct population size over thousands of generations, using a new class of algorithms [sequentially Markovian coalescent (SMC) methods]. These analyses often show a recent decline in N_e (effective size), which at face value implies a conservation or demographic crisis: a population crash and loss of genetic diversity. This interpretation is frequently mistaken. Here we outline how SMC methods work, why they generate this misleading signal, and suggest simple approaches for exploiting the rich information produced by these algorithms. In most species, genomic patterns reflect major changes in the species' range and subdivision over tens or hundreds of thousands of years. Consequently, collaboration between geneticists, palaeoecologists, palaeoclimatologists, and geologists is crucial for evaluating the outputs of SMC algorithms.

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain. The integration of single-cell technologies with genome-wide association studies (GWAS) and transcriptomic data has further advanced our understanding of cell-specific chromatin dynamics. This review discusses recent findings regarding the role played by chromatin accessibility in brain disease, highlighting the need for high-quality data and rigorous computational tools. Future directions include spatial chromatin studies and CRISPR-based functional validation to bridge genetic discovery and clinical applications, paving the way for targeted gene-regulatory therapies.

N6-methyladenosine (m6A) regulates retrotransposon activity, shifting between repression and activation across different species and developmental stages. It promotes RNA decay, sequestration, or stability, influencing genome integrity, adaptation, and disease. This article explores the dual role of m6A in retrotransposon control, highlighting its evolutionary significance in genome regulation and cellular differentiation.