Trends in Genetics最新文献

Poly(ADP-ribose) polymerase 1 (PARP1) is a crucial member of the PARP family, which modifies targets through ADP-ribosylation and plays key roles in a variety of biological processes. PARP inhibitors (PARPis) hinder ADP-ribosylation and lead to the retention of PARP1 at the DNA lesion (also known as trapping), which underlies their toxicity. However, inhibitors and mutations that make PARP1 inactive do not necessarily correlate with trapping potency, challenging the current understanding of inactivation-caused trapping. Recent studies on mouse models indicate that both trapping and non-trapping inactivating mutations of PARP1 lead to embryonic lethality, suggesting the unexpected toxicity of the current inhibition strategy. The allosteric model, complicated automodification, and various biological functions of PARP1 all contribute to the complexity of PARP1 inactivation.

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.

This review comprehensively examines the molecular biology and genetic origins of cellular senescence. We focus on various cellular stressors and pathways leading to senescence, including recent advances in the understanding of the genetic influences driving senescence, such as telomere attrition, chemotherapy-induced DNA damage, pathogens, oncogene activation, and cellular and metabolic stress. This review also highlights the complex interplay of various signaling and metabolic pathways involved in cellular senescence and provides insights into potential therapeutic targets for aging-related diseases. Furthermore, this review outlines future research directions to deepen our understanding of senescence biology and develop effective interventions targeting senescent cells (SnCs).

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.

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.

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.

Lasso peptides are a large and sequence-diverse class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products characterized by their slip knot-like shape. These unique, highly stable peptides are produced by bacteria for various purposes. Their stability and sequence diversity make them a potentially useful scaffold for biomedically relevant folded peptides. However, many questions remain about lasso peptide biosynthesis, ecological function, and diversification potential for biomedical and agricultural applications. This review discusses new insights and open questions about lasso peptide biosynthesis and biological function. The role that genome mining has played in the development of new methodologies for discovering and diversifying lasso peptides is also discussed.

Adaptive evolution often involves structural variation affecting genes or cis-regulatory changes that engender novel and favorable gain-of-function gene regulation. Such mutation could result in a favorable dominant trait. At the same time, the gene product could be dosage sensitive if its change in concentration disrupts another trait. As a result, the mutant allele would display dosage-sensitive pleiotropy (DSP). By minimizing imbalance while conserving the favorable dominant effect, heterozygosity can increase fitness and result in heterosis. The properties of these alleles are consistent with evidence from multiple studies that indicate increased fitness of heterozygous regulatory mutations. DSP can help explain mysterious properties of heterosis as well as other effects of hybridization.

There is an urgent need to improve wheat for upcoming challenges, including biotic and abiotic stresses. Sustainable wheat improvement requires the introduction of new genes and alleles in high-yielding wheat cultivars. Using new approaches, tools, and technologies to identify and introduce new genes in wheat cultivars is critical. High-quality genomes, transcriptomes, and pangenomes provide essential resources and tools to examine wheat closely to identify and manipulate new and targeted genes and alleles. Wheat genomics has improved excellently in the past 5 years, generating multiple genomes, pangenomes, and transcriptomes. Leveraging these resources allows us to accelerate our crop improvement pipelines. This review summarizes the progress made in wheat genomics and trait discovery in the past 5 years.