Annual review of genetics最新文献

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. Recent advances in molecular and genomic characterization have revealed symbiosis-specific genes and mechanisms shared among symbiotic cnidarians. In this review, we focus on the cellular and molecular processes that underpin the interaction between symbiont and host. We discuss symbiont acquisition via phagocytosis, modulation of host innate immunity, symbiont integration into host cell metabolism, and nutrient exchange as a fundamental aspect of stable symbiotic associations. We emphasize the importance of using model systems to dissect the cellular complexity of endosymbiosis, which ultimately serves as the basis for understanding its ecology and capacity to adapt in the face of climate change.

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. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.

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. We summarize the particular challenges presented by each organ system and describe how iPSC models are being used to address them. Finally, we discuss emerging iPSC-derived organoid models and the potential value that they can bring to studies of human disease.

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. Even unicellular organisms age at a cellular level, demonstrating that cellular aging is inevitable. Extensive studies in yeast have established the framework of how asymmetric cell division and gametogenesis may contribute to the resetting of cellular age. This review examines the mechanisms of germline immortality-how germline cells reset the aging of cells-drawing a parallel between yeast and multicellular organisms.

The raison d'être of meiosis is shuffling of genetic information via Mendelian segregation and, within individual chromosomes, by DNA crossing-over. These outcomes are enabled by a complex cellular program in which interactions between homologous chromosomes play a central role. We first provide a background regarding the basic principles of this program. We then summarize the current understanding of the DNA events of recombination and of three processes that involve whole chromosomes: homolog pairing, crossover interference, and chiasma maturation. All of these processes are implemented by direct physical interaction of recombination complexes with underlying chromosome structures. Finally, we present convergent lines of evidence that the meiotic program may have evolved by coupling of this interaction to late-stage mitotic chromosome morphogenesis.

Organismal development requires the reproducible unfolding of an ordered sequence of discrete steps (cell fate determination, migration, tissue folding, etc.) in both time and space. Here, we review the mechanisms that grant temporal specificity to developmental steps, including molecular clocks and timers. Individual timing mechanisms must be coordinated with each other to maintain the overall developmental sequence. However, phenotypic novelties can also arise through the modification of temporal patterns over the course of evolution. Two main types of variation in temporal patterning characterize interspecies differences in developmental time: allochrony, where the overall developmental sequence is either accelerated or slowed down while maintaining the relative duration of individual steps, and heterochrony, where the duration of specific developmental steps is altered relative to the rest. New advances in in vitro modeling of mammalian development using stem cells have recently enabled the revival of mechanistic studies of allochrony and heterochrony. In both cases, differences in the rate of basic cellular functions such as splicing, translation, protein degradation, and metabolism seem to underlie differences in developmental time. In the coming years, these studies should identify the genetic differences that drive divergence in developmental time between species.

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. We address work from both model organisms and mammalian systems but predominantly focus on multicellular eukaryotes owing to the additional complexities inherent in the coordination of replication and transcription in the context of cell type-specific gene expression and higher-order chromatin organization.

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. Selection, gene flow, and hybridization have played and will continue to play an important role in the adaptation or extinction of coral reef taxa in the face of rapid environmental change, but research remains exceptionally limited compared to the urgent needs. Critical areas for future investigation include understanding evolutionary potential and the mechanisms of local adaptation, developing historical baselines, and building greater research capacity in the countries where most reef diversity is concentrated.

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. The genetic causes of SAIDs are complex and include both germline and somatic pathogenic variants that affect various inflammatory signaling pathways. We provide an overview of the acquired SAIDs from a genetic perspective and summarize the clinical phenotypes and mechanism(s) of inflammation, aiming to provide a comprehensive understanding of the pathogenesis of autoinflammatory diseases.

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.