Consensus holds that most cells in the embryo are genetically identical and have healthy genomes. However, embryonic cells with abnormal chromosomes are surprisingly frequent. In a recent publication, de Jaime-Soguero et al. report that extracellular developmental signaling pathways, including BMP, FGF, and WNT, can promote or prevent chromosome instability in certain cell types.

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.

In a recent article in Nature Cell Biology, Eroglu et al. link heritable, environment-induced epigenetic germline feminization to the accumulation, transmission, and replication of amyloid particles in Caenorhabditis elegans.

Polycomb repressive complex 1 (PRC1) is an essential repressor of lineage-specific genes central to the establishment and preservation of cellular identity. Recent findings by Szczurek et al. show that the noncanonical form of PRC1 (ncPRC1), which mediates H2AK119ub1, promotes a deep OFF state at promoters by blocking transcription initiation.

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.

As a noninvasive biomarker, cell-free DNA (cfDNA) has achieved remarkable success in clinical applications. Notably, cfDNA is essentially DNA, and conducting whole-genome sequencing (WGS) can yield a wealth of genetic information. These invaluable data should not be confined to one-time use; instead, they should be leveraged for more comprehensive population genetic analysis, including genetic variation spectrum, population structure and genetic selection, and genome-wide association studies (GWASs), among others. Such research findings can, in turn, facilitate clinical practice, enabling more advanced and accurate disease predictions. This review explores the advantages, challenges, and current research areas of cfDNA in population genetics. We hope that this review can serve as a new chapter in the repurposing of cfDNA sequence data generated from clinical testing in population genetics.

Insect male genitalia are among the fastest evolving structures of animals. Studying these changes among closely related species represents a powerful approach to dissect developmental processes and genetic mechanisms underlying phenotypic diversification and the underlying evolutionary drivers. Here, we review recent breakthroughs in understanding the developmental and genetic bases of the evolution of genital organs among Drosophila species and other insects. This work has helped reveal how tissue and organ size evolve and understand the appearance of morphological novelties, and how these phenotypic changes are generated through altering gene expression and redeployment of gene regulatory networks. Future studies of genital evolution in Drosophila and a wider range of insects hold great promise to help understand the specification, differentiation, and diversification of organs more generally.

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.

Hundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5' leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated, while characterised smORF functions have risen from anecdotal to identifiable trends: smORFs can either have a cis-noncoding regulatory function (involving low translation of nonfunctional peptides) or full coding function mediated by robustly translated peptides, often having cellular and physiological roles as membrane-associated regulators of canonical proteins. The evolutionary context reveals that many smORFs represent new genes emerging de novo from noncoding sequences. We suggest a mechanism for this process, where cis-noncoding smORF functions provide niches for the subsequent evolution of full peptide functions.

The genetic clock is a well-established tool used in evolutionary biology for estimating divergence times between species, individuals, or cells based on DNA sequence changes. Yu et al. have revisited the clock to make it applicable to clonal multicellular organisms that expand through asexual reproduction mechanisms, enabling more comprehensive evolutionary tracking.

The process of sexual development in animals is modulated by a variety of mechanisms. Some species respond to environmental cues, while, in others, sex determination is thought to be controlled by a single 'master regulator' gene. However, many animals respond to a combination of environmental cues (e.g., temperature) and genetic factors (e.g., sex chromosomes). Even among species in which genetic factors predominate, there is a continuum between monofactorial and polygenic systems. The perception that polygenic systems are rare may result from experiments that lack the statistical power to detect multiple loci. Intellectual biases against the existence of polygenic sex determination (PSD) may further arise from misconceptions about the regulation of developmental processes and a misreading of theoretical results on the stability of polygenic systems of sex determination.

Introgression with archaic hominins and subsequent natural selection has shaped the immune system of modern humans. Recently, Sun et al. investigated the immunity advantages of a Neanderthalic variant in the membrane-bound immunoglobulin G1 (IGHG1) gene, activating pathogen-specific antibody production toward modern threats yet conversely increasing the risk of autoimmune diseases.

Why is it that the X chromosome that comes from the male parent is inactivated in female marsupials, female mice, and even female mealy bugs, or the whole paternal chromosome complement in some weird flies? A new paper by Milton et al. now reveals DNA methylation patterns established in the male germline before meiosis in wallabies that may constitute the elusive paternal imprint.

This review addresses the significant challenge of identifying causal genetic variants within quantitative trait loci (QTLs) for complex traits and diseases. Despite progress in detecting the ever-larger number of such loci, establishing causality remains daunting. We advocate for integrating bioinformatics and multiomics analyses to streamline the prioritization of candidate genes' variants. Our case study on the Pla2g4e gene, identified previously as a positional candidate obesity gene through genetic mapping and expression studies, demonstrates how applying multiomic data filtered through regulatory elements containing SNPs can refine the search for causative variants. This approach can yield results that guide more efficient experimental strategies, accelerating genetic research toward functional validation and therapeutic development.

The extraordinary diversity and adaptive fit of organisms to their environment depends fundamentally on the availability of variation. While most population genetic frameworks assume that random mutations produce isotropic phenotypic variation, the distribution of variation available to natural selection is more restricted, as the distribution of phenotypic variation is affected by a range of factors in developmental systems. Here, we revisit the concept of developmental bias - the observation that the generation of phenotypic variation is biased due to the structure, character, composition, or dynamics of the developmental system - and argue that a more rigorous investigation into the role of developmental bias in the genotype-to-phenotype map will produce fundamental insights into evolutionary processes, with potentially important consequences on the relation between micro- and macro-evolution. We discuss the hierarchical relationships between different types of variational biases, including mutation bias and developmental bias, and their roles in shaping the realized phenotypic space. Furthermore, we highlight the challenges in studying variational bias and propose potential approaches to identify developmental bias using modern tools.

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.

'Epigenetics' is the process by which distinct cell types or cell states are inherited through multiple cell divisions. 'Epigenomics' refers to DNA-associated physical and functional entities including histone modifications and DNA methylation, not concepts of inheritance. Conflating epigenetics and epigenomics is confusing and causes misunderstanding of a fundamental biological process.

Recent studies have addressed the relevance of phase separation, by which membrane-less compartments are formed within the nucleus, to understand the impact of genetic variants. They highlight unsuspected links between phase separation and haploinsufficiency of transcription factors.

Crossing over between homologous chromosomes in meiosis is essential in most eukaryotes to produce gametes with the correct ploidy. Meiotic crossovers are typically evenly spaced, with each homolog pair receiving at least one crossover. The association of crossovers with distal sister chromatid cohesion is critical for the proper segregation of homologs in the first meiotic division. Studies in baker's yeast (Saccharomyces cerevisiae) have shown that meiotic crossovers result primarily from the biased resolution of double Holliday junction (dHJ) recombination intermediates through the actions of factors that belong to the DNA mismatch repair family. These findings and studies involving fine-scale mapping of meiotic crossover events have led to a new generation of mechanistic models for crossing over that are currently being tested.

How genotype determines phenotype is a well-explored question, but genotype-environment interactions and their heritable impact on phenotype over the course of evolution are not as thoroughly investigated. The fish Astyanax mexicanus, comprising surface and cave ecotypes, is an ideal emerging model to study the genetic basis of adaptation to new environments. This model has permitted quantitative trait locus (QTL) mapping and whole-genome comparisons to identify the genetic bases of traits such as albinism and insulin resistance and has helped in the better understanding of fundamental evolutionary mechanisms. In this review, we summarize recent advances in A. mexicanus genetics and discuss its broader impact on the fields of adaptation and evolutionary genetics.

RNA functions by interacting with its intended targets structurally. However, due to the dynamic nature of RNA molecules, RNA structures are difficult to determine experimentally or predict computationally. Artificial intelligence (AI) has revolutionized many biomedical fields and has been progressively utilized to deduce RNA structures, target binding, and associated functionality. Integrating structural and target binding information could also help improve the robustness of AI-based RNA function prediction and RNA design. Given the rapid development of deep learning (DL) algorithms, AI will provide an unprecedented opportunity to elucidate the sequence-structure-function relation of RNAs.