1,181 results match your criteria: "Annual Review Of Genetics[Journal]"

RNA Repair: Hiding in Plain Sight.

Annu Rev Genet

November 2023

Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; email:

Enzymes that phosphorylate, dephosphorylate, and ligate RNA 5' and 3' ends were discovered more than half a century ago and were eventually shown to repair purposeful site-specific endonucleolytic breaks in the RNA phosphodiester backbone. The pace of discovery and characterization of new candidate RNA repair activities in taxa from all phylogenetic domains greatly exceeds our understanding of the biological pathways in which they act. The key questions anent RNA break repair in vivo are () identifying the triggers, agents, and targets of RNA cleavage and () determining whether RNA repair results in restoration of the original RNA, modification of the RNA (by loss or gain at the ends), or rearrangements of the broken RNA segments (i.

View Article and Find Full Text PDF

Symbiotic interactions occur in all domains of life, providing organisms with resources to adapt to new habitats. A prime example is the endosymbiosis between corals and photosynthetic dinoflagellates. Eukaryotic dinoflagellate symbionts reside inside coral cells and transfer essential nutrients to their hosts, driving the productivity of the most biodiverse marine ecosystem.

View Article and Find Full Text PDF

Manipulating the Destiny of Wild Populations Using CRISPR.

Annu Rev Genet

November 2023

Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA; email:

Genetic biocontrol aims to suppress or modify populations of species to protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge in research in this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on the current state of CRISPR technologies for genetic biocontrol of pests and highlights the progress and ongoing challenges of using these approaches.

View Article and Find Full Text PDF

Induced Pluripotent Stem Cells in Disease Biology and the Evidence for Their In Vitro Utility.

Annu Rev Genet

November 2023

Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA; email:

Many human phenotypes are impossible to recapitulate in model organisms or immortalized human cell lines. Induced pluripotent stem cells (iPSCs) offer a way to study disease mechanisms in a variety of differentiated cell types while circumventing ethical and practical issues associated with finite tissue sources and postmortem states. Here, we discuss the broad utility of iPSCs in genetic medicine and describe how they are being used to study musculoskeletal, pulmonary, neurologic, and cardiac phenotypes.

View Article and Find Full Text PDF

Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health.

View Article and Find Full Text PDF

Integrating Complex Life Cycles in Comparative Developmental Biology.

Annu Rev Genet

November 2023

Department of Biology, Hopkins Marine Station, Stanford University, Pacific Grove, California, USA; email:

The goal of comparative developmental biology is identifying mechanistic differences in embryonic development between different taxa and how these evolutionary changes have led to morphological and organizational differences in adult body plans. Much of this work has focused on direct-developing species in which the adult forms straight from the embryo and embryonic modifications have direct effects on the adult. However, most animal lineages are defined by indirect development, in which the embryo gives rise to a larval body plan and the adult forms by transformation of the larva.

View Article and Find Full Text PDF

Finding Needles in the Haystack: Strategies for Uncovering Noncoding Regulatory Variants.

Annu Rev Genet

November 2023

Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA; email:

Despite accumulating evidence implicating noncoding variants in human diseases, unraveling their functionality remains a significant challenge. Systematic annotations of the regulatory landscape and the growth of sequence variant data sets have fueled the development of tools and methods to identify causal noncoding variants and evaluate their regulatory effects. Here, we review the latest advances in the field and discuss potential future research avenues to gain a more in-depth understanding of noncoding regulatory variants.

View Article and Find Full Text PDF

The ease and throughput of single-cell genomics have steadily improved, and its current trajectory suggests that surveying single-cell populations will become routine. We discuss the merger of quantitative genetics with single-cell genomics and emphasize how this synergizes with advantages intrinsic to plants. Single-cell population genomics provides increased detection resolution when mapping variants that control molecular traits, including gene expression or chromatin accessibility.

View Article and Find Full Text PDF

Systemic autoinflammatory diseases (SAIDs) are a heterogeneous group of disorders caused by excess activation of the innate immune system in an antigen-independent manner. Starting with the discovery of the causal gene for familial Mediterranean fever, more than 50 monogenic SAIDs have been described. These discoveries, paired with advances in immunology and genomics, have allowed our understanding of these diseases to improve drastically in the last decade.

View Article and Find Full Text PDF

Assigning functions to genes and learning how to control their expression are part of the foundation of cell biology and therapeutic development. An efficient and unbiased method to accomplish this is genetic screening, which historically required laborious clone generation and phenotyping and is still limited by scale today. The rapid technological progress on modulating gene function with CRISPR-Cas and measuring it in individual cells has now relaxed the major experimental constraints and enabled pooled screening with complex readouts from single cells.

View Article and Find Full Text PDF

Asymmetric Stem Cell Division and Germline Immortality.

Annu Rev Genet

November 2023

Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; email:

Germ cells are the only cell type that is capable of transmitting genetic information to the next generation, which has enabled the continuation of multicellular life for the last 1.5 billion years. Surprisingly little is known about the mechanisms supporting the germline's remarkable ability to continue in this eternal cycle, termed germline immortality.

View Article and Find Full Text PDF

Transcription-Replication Conflicts as a Source of Genome Instability.

Annu Rev Genet

November 2023

Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA; email:

Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA sequence. Conflicts between the replication and transcription machineries (transcription-replication conflicts, or TRCs) are widespread in both prokaryotes and eukaryotes and have the capacity to both cause DNA damage and compromise complete, faithful replication of the genome. This review will highlight recent studies investigating the genomic locations of TRCs and the mechanisms by which they may be prevented, mitigated, or resolved.

View Article and Find Full Text PDF

Mechanisms Underlying the Formation and Evolution of Vertebrate Color Patterns.

Annu Rev Genet

November 2023

Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA; email:

Vertebrates exhibit a wide range of color patterns, which play critical roles in mediating intra- and interspecific communication. Because of their diversity and visual accessibility, color patterns offer a unique and fascinating window into the processes underlying biological organization. In this review, we focus on describing many of the general principles governing the formation and evolution of color patterns in different vertebrate groups.

View Article and Find Full Text PDF

Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, throughout health, injury, and disease. Recent transcriptomic studies have identified gene transcript signatures expressed by microglia that may provide the foundation for unprecedented insights into their functions.

View Article and Find Full Text PDF

Coral Reef Population Genomics in an Age of Global Change.

Annu Rev Genet

November 2023

Department of Ecology, Evolution, and Natural Resources, Rutgers University, New Brunswick, New Jersey, USA.

Coral reefs are both exceptionally biodiverse and threatened by climate change and other human activities. Here, we review population genomic processes in coral reef taxa and their importance for understanding responses to global change. Many taxa on coral reefs are characterized by weak genetic drift, extensive gene flow, and strong selection from complex biotic and abiotic environments, which together present a fascinating test of microevolutionary theory.

View Article and Find Full Text PDF

Quiescence in .

Annu Rev Genet

November 2022

Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA; email:

Most cells live in environments that are permissive for proliferation only a small fraction of the time. Entering quiescence enables cells to survive long periods of nondivision and reenter the cell cycle when signaled to do so. Here, we describe what is known about the molecular basis for quiescence in , with emphasis on the progress made in the last decade.

View Article and Find Full Text PDF

Within the life cycle of a living organism, another life cycle exists for the selfish genome inhabitants, which are called transposable elements (TEs). These mobile sequences invade, duplicate, amplify, and diversify within a genome, increasing the genome's size and generating new mutations. Cells act to defend their genome, but rather than permanently destroying TEs, they use chromatin-level repression and epigenetic inheritance to silence TE activity.

View Article and Find Full Text PDF

A Half Century Defining the Logic of Cellular Life.

Annu Rev Genet

November 2022

Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA; email:

Over more than fifty years, I have studied how the logic that controls and integrates cell function is built into the dynamic architecture of living cells. I worked with a succession of exceptionally talented students and postdocs, and we discovered that the bacterial cell is controlled by an integrated genetic circuit in which transcriptional and translational controls are interwoven with the three-dimensional deployment of key regulatory and morphological proteins. 's interconnected genetic regulatory network includes logic that regulates sets of genes expressed at specific times in the cell cycle and mechanisms that synchronize the advancement of the core cyclical circuit with chromosome replication and cytokinesis.

View Article and Find Full Text PDF

Spermatogenesis is a complex differentiation process coordinated spatiotemporally across and along seminiferous tubules. Cellular heterogeneity has made it challenging to obtain stage-specific molecular profiles of germ and somatic cells using bulk transcriptomic analyses. This has limited our ability to understand regulation of spermatogenesis and to integrate knowledge from model organisms to humans.

View Article and Find Full Text PDF

Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome. When HARs were discovered in 2006, their function was mysterious due to scant annotation of the noncoding genome. Diverse technologies, from transgenic animals to machine learning, have consistently shown that HARs function as gene regulatory enhancers with significant enrichment in neurodevelopment.

View Article and Find Full Text PDF

Scalable sequence-function studies have enabled the systematic analysis and cataloging of hundreds of thousands of coding and noncoding genetic variants in the human genome. This has improved clinical variant interpretation and provided insights into the molecular, biophysical, and cellular effects of genetic variants at an astonishing scale and resolution across the spectrum of allele frequencies. In this review, we explore current applications and prospects for the field and outline the principles underlying scalable functional assay design, with a focus on the study of single-nucleotide coding and noncoding variants.

View Article and Find Full Text PDF

Mechanisms Underlying Circuit Dysfunction in Neurodevelopmental Disorders.

Annu Rev Genet

November 2022

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Recent advances in genomics have revealed a wide spectrum of genetic variants associated with neurodevelopmental disorders at an unprecedented scale. An increasing number of studies have consistently identified mutations-both inherited and de novo-impacting the function of specific brain circuits. This suggests that, during brain development, alterations in distinct neural circuits, cell types, or broad regulatory pathways ultimately shaping synapses might be a dysfunctional process underlying these disorders.

View Article and Find Full Text PDF

The Four Causes: The Functional Architecture of Centromeres and Kinetochores.

Annu Rev Genet

November 2022

The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; email:

Kinetochores are molecular machines that power chromosome segregation during the mitotic and meiotic cell divisions of all eukaryotes. Aristotle explains how we think we have knowledge of a thing only when we have grasped its cause. In our case, to gain understanding of the kinetochore, the four causes correspond to questions that we must ask: () What are the constituent parts, () how does it assemble, () what is the structure and arrangement, and () what is the function? Here we outline the current blueprint for the assembly of a kinetochore, how functions are mapped onto this architecture, and how this is shaped by the underlying pericentromeric chromatin.

View Article and Find Full Text PDF

Transcription-Translation Coupling in Bacteria.

Annu Rev Genet

November 2022

Wadsworth Center, New York State Department of Health, Albany, New York, USA; email:

In bacteria, transcription and translation take place in the same cellular compartment. Therefore, a messenger RNA can be translated as it is being transcribed, a process known as transcription-translation coupling. This process was already recognized at the dawn of molecular biology, yet the interplay between the two key players, the RNA polymerase and ribosome, remains elusive.

View Article and Find Full Text PDF