Trends in Genetics最新文献

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.

In eukaryotic cells, DNA is wrapped around histone octamers to compact the genome. Although such compaction is required for the precise segregation of the genome during cell division, it restricts the DNA-protein interactions essential for several cellular processes. During meiosis, a specialized cell division process that produces gametes, several DNA-protein interactions are crucial for assembling meiosis-specific chromosome structures, meiotic recombination, chromosome segregation, and transcriptional regulation. The role of chromatin remodelers (CRs) in facilitating DNA-protein transactions during mitosis is well appreciated, whereas how they facilitate meiosis-specific processes is poorly understood. In this review, we summarize experimental evidence supporting the role of CRs in meiosis in various model systems and suggest future perspectives to advance the field.

DNA double-strand break (DSB) induction leads to local transcriptional silencing at damage sites, raising the question: Why are RNA processing factors (RPFs), including splicing factors, rapidly recruited to these sites? Recent findings show that DSBs cluster in a chromatin compartment termed the 'D compartment', where DNA damage response (DDR) genes relocate and undergo transcriptional activation. Here, we propose two non-mutually exclusive models to elucidate the rationale behind the recruitment of RPFs to DSB sites. First, RPFs circulate through the D compartment to process transcripts of the relocated DDR genes. Second, the D compartment serves as a 'post-translational modifications (PTMs) hub', altering RPF activity and leading to the production of unique DNA damage-induced transcripts, which are essential for orchestrating the DDR.

Evolutionary medicine, which integrates evolutionary biology and medicine, significantly enhances our understanding of human traits and disease susceptibility. However, previous studies in this field have often focused on single-nucleotide variants due to technological limitations in characterizing complex genomic regions, hindering the comprehensive analyses of their evolutionary origins and clinical significance. In this review, we summarize recent advancements in complete telomere-to-telomere (T2T), primate genomes and other primate resources, and illustrate how these resources facilitate the research of complex regions. We focus on several biomedically relevant regions to examine the relationship between primate genome evolution and human diseases. We also highlight the potentials of high-throughput functional genomic technologies for assessing candidate loci. Finally, we discuss future directions for primate research within the context of evolutionary medicine.

Inbreeding depression and genetic rescue are central themes in conservation biology. Translocation is a tool to assist genetic rescue but is connected to risks. A new study by Quinn et al. used genomic data to evaluate translocations as a potential action in montane red fox, bringing important implications also for other threatened species.

While the cost of genome sequencing has decreased, -80°C DNA preservation and raw sequence data archiving remain expensive. Transitioning to room-temperature DNA preservation could reduce costs, lessen researchers' reliance on the electrical grid, and encourage a future proofing strategy of periodical updating with higher quality sequencing instead of long-term storage of raw signal data. A new technology recently described by Prince et al. that could help realize these goals is Thermoset-REinforced Xeropreservation (T-REX).

DNA inversions in bacteria were known to create diversity through intergenic or partial intergenic changes. Now, Chanin, West, et al. reveal intragenic inversions, enabling single genes to encode multiple protein variants via sequence recoding or truncation - an unexpected mechanism for expanding protein diversity without increasing genome size.

Research into aging constitutes a pivotal endeavor aimed at elucidating the underlying biological mechanisms governing aging and age-associated diseases, as well as promoting healthy longevity. Recent advances in transcriptomic technologies, such as bulk RNA sequencing (RNA-seq), single-cell transcriptomics, and spatial transcriptomics, have revolutionized our ability to study aging at unprecedented resolution and scale. These technologies present novel opportunities for the discovery of biomarkers, elucidation of molecular pathways, and development of targeted therapeutic strategies for age-related disorders. This review surveys recent breakthroughs in different types of transcripts on aging, such as mRNA, long noncoding (lnc)RNA, tRNA, and miRNA, highlighting key findings and discussing their potential implications for future studies in this field.

The onset and progression of dominant diseases are thought to result from haploinsufficiency or dominant negative effects. Here, we propose transcriptional adaptation (TA), a newly identified response to mRNA decay, as an additional cause of some dominant diseases. TA modulates the expression of so-called adapting genes, likely via mRNA decay products, resulting in genetic compensation or a worsening of the phenotype. Recent studies have challenged the current concepts of haploinsufficiency or poison proteins as the mechanisms underlying certain dominant diseases, including Brugada syndrome, hypertrophic cardiomyopathy, and frontotemporal lobar degeneration. We hypothesize that for these and other dominant diseases, when the underlying mutation leads to mRNA decay, the phenotype is due at least partly to the dysregulation of gene expression via TA.