Advances in Genetics最新文献

Extracellular vesicles (EVs) are membrane-enclosed particles that are secreted by nearly all cells and play an important role in intercellular communication by transporting protein and nucleic acids between cells. EV-mediated processes shape phenomena as diverse as cancer progression, immune function, and wound healing. The natural role of EVs in encapsulating and delivering cargo to modify cellular function highlights the potential to use these particles as therapeutic delivery vehicles. In this chapter, we describe emerging strategies for EV engineering and consider how different approaches to EV production, purification, and design may impact the efficacy of EV-based therapeutics.

The 200years of research efforts on Parkinson disease (PD) form the basis of our understanding of the second most common neurodegenerative disorder after Alzheimer disease. This journey has been marked by the revolutionary discovery of a neurotransmitter replacement therapy that provides a longer and healthier life to patients. Since 1997, the advances in the genetics of PD have expanded our understanding of this neurodegenerative disorder and they are opening up new ways to search for disease-modifying therapies. This chapter is a summary of the historical discoveries and latest progress in PD research.

Most living organisms on earth experience daily and expected changes from the rotation of the earth. For an organism, the ability to predict and prepare for incoming stresses or resources is a very important skill for survival. This cellular process of measuring daily time of the day is collectively called the circadian clock. Because of its fundamental role in survival in nature, there is a great interest in studying the natural variation of the circadian clock. However, characterizing the genetic and molecular mechanisms underlying natural variation of circadian clocks remains a challenging task. In this chapter, we will summarize the progress in studying natural variation of the circadian clock in the successful eukaryotic model Neurospora, which led to discovering many design principles of the molecular mechanisms of the eukaryotic circadian clock. Despite the success of the system in revealing the molecular mechanisms of the circadian clock, Neurospora has not been utilized to extensively study natural variation. We will review the challenges that hindered the natural variation studies in Neurospora, and how they were overcome. We will also review the advantages of Neurospora for natural variation studies. Since Neurospora is the model fungal species for circadian study, it represents over 5 million species of fungi on earth. These fungi play important roles in ecosystems on earth, and as such Neurospora could serve as an important model for understanding the ecological role of natural variation in fungal circadian clocks.

Fungi are possibly the most diverse eukaryotic kingdom, with over a million member species and an evolutionary history dating back a billion years. Fungi have been at the forefront of eukaryotic genomics, and owing to initiatives like the 1000 Fungal Genomes Project the amount of fungal genomic data has increased considerably over the last 5 years, enabling large-scale comparative genomics of species across the kingdom. In this chapter, we first review fungal evolution and the history of fungal genomics. We then review in detail seven phylogenomic methods and reconstruct the phylogeny of 84 fungal species from 8 phyla using each method. Six methods have seen extensive use in previous fungal studies, while a Bayesian supertree method is novel to fungal phylogenomics. We find that both established and novel phylogenomic methods can accurately reconstruct the fungal kingdom. Finally, we discuss the accuracy and suitability of each phylogenomic method utilized.

Seasonal change in the temperate and polar regions of Earth determines how the world looks around us and, in fact, how we live our day-to-day lives. For biological organisms, seasonal change typically involves complex physiological and metabolic reorganization, the majority of which is regulated by photoperiodism. Photoperiodism is the ability of animals and plants to use day length or night length, resulting in life-historical transformations, including seasonal development, migration, reproduction, and dormancy. Seasonal timing determines not only survival and reproductive success but also the structure and organization of complex communities and, ultimately, the biomes of Earth. Herein, a small mosquito, Wyeomyia smithii, that lives only in the water-filled leaves of a carnivorous plant over a wide geographic range, is used to explore the genetic and evolutionary basis of photoperiodism. Photoperiodism in W. smithii is considered in the context of its historical biogeography in nature to examine the startling finding that recent rapid climate change can drive genetic change in plants and animals at break-neck speed, and to challenge the ponderous 80+ year search for connections between daily and seasonal time-keeping mechanisms. Finally, a model is proposed that reconciles the seemingly disparate 24-h daily clock driven by the invariant rotation of Earth about its axis with the evolutionarily flexible seasonal timer orchestrated by variable seasonality driven by the rotation of Earth about the Sun.

Fusarium oxysporum is a large species complex of both plant and human pathogens that attack a diverse array of species in a host-specific manner. Comparative genomic studies have revealed that the host-specific pathogenicity of the F. oxysporum species complex (FOSC) was determined by distinct sets of supernumerary (SP) chromosomes. In contrast to common vertical transfer, where genetic materials are transmitted via cell division, SP chromosomes can be transmitted horizontally between phylogenetic lineages, explaining the polyphyletic nature of the host-specific pathogenicity of the FOSC. The existence of a diverse array of SP chromosomes determines the broad host range of this species complex, while the conserved core genome maintains essential house-keeping functions. Recognition of these SP chromosomes enables the functional and structural compartmentalization of F. oxysporum genomes. In this review, we examine the impact of this group of cross-kingdom pathogens on agricultural productivity and human health. Focusing on the pathogenicity of F. oxysporum in the phylogenomic framework of the genus Fusarium, we elucidate the evolution of pathogenicity within the FOSC. We conclude that a population genomics approach within a clearly defined phylogenomic framework is essential not only for understanding the evolution of the pathogenicity mechanism but also for identifying informative candidates associated with pathogenicity that can be developed as targets in disease management programs.

Individualized medicine, or the tailoring of therapeutic interventions to a patient's unique genetic, biochemical, physiological, exposure and behavioral profile, has been enhanced, if not enabled, by modern biomedical technologies such as high-throughput DNA sequencing platforms, induced pluripotent stem cell assays, biomarker discovery protocols, imaging modalities, and wireless monitoring devices. Despite successes in the isolated use of these technologies, however, it is arguable that their combined and integrated use in focused studies of individual patients is the best way to not only tailor interventions for those patients, but also shed light on treatment strategies for patients with similar conditions. This is particularly true for individuals with rare diseases since, by definition, they will require study without recourse to other individuals, or at least without recourse to many other individuals. Such integration and focus will require new biomedical scientific paradigms and infrastructure, including the creation of databases harboring study results, the formation of dedicated multidisciplinary research teams and new training programs. We consider the motivation and potential for such integration, point out areas in need of improvement, and argue for greater emphasis on improving patient health via technological innovations, not merely improving the technologies themselves. We also argue that the paradigm described can, in theory, be extended to the study of individuals with more common diseases.

Metabolic gene clusters (MGCs) have provided some of the earliest glimpses at the biochemical machinery of yeast and filamentous fungi. MGCs encode diverse genetic mechanisms for nutrient acquisition and the synthesis/degradation of essential and adaptive metabolites. Beyond encoding the enzymes performing these discrete anabolic or catabolic processes, MGCs may encode a range of mechanisms that enable their persistence as genetic consortia; these include enzymatic mechanisms to protect their host fungi from their inherent toxicities, and integrated regulatory machinery. This modular, self-contained nature of MGCs contributes to the metabolic and ecological adaptability of fungi. The phylogenetic and ecological patterns of MGC distribution reflect the broad diversity of fungal life cycles and nutritional modes. While the origins of most gene clusters are enigmatic, MGCs are thought to be born into a genome through gene duplication, relocation, or horizontal transfer, and analyzing the death and decay of gene clusters provides clues about the mechanisms selecting for their assembly. Gene clustering may provide inherent fitness advantages through metabolic efficiency and specialization, but experimental evidence for this is currently limited. The identification and characterization of gene clusters will continue to be powerful tools for elucidating fungal metabolism as well as understanding the physiology and ecology of fungi.

The genetic material, contained on chromosomes, is often described as the "blueprint for life." During nuclear division, the chromosomes are pulled into each of the two daughter nuclei by the coordination of spindle microtubules, kinetochores, centromeres, and chromatin. These four functional units must link the chromosomes to the microtubules, signal to the cell when the attachment is made so that division can proceed, and withstand the force generated by pulling the chromosomes to either daughter cell. To perform each of these functions, kinetochores are large protein complexes, approximately 5MDa in size, and they contain at least 45 unique proteins. Many of the central components in the kinetochore are well conserved, yielding a common core of proteins forming consistent structures. However, many of the peripheral subcomplexes vary between different taxonomic groups, including changes in primary sequence and gain or loss of whole proteins. It is still unclear how significant these changes are, and answers to this question may provide insights into adaptation to specific lifestyles or progression of disease that involve chromosome instability.