Advances in Genetics

An unprecedented number of pathogenic fungi are emerging and causing disease in animals and plants, putting the resilience of wild and managed ecosystems in jeopardy. While the past decades have seen an increase in the number of pathogenic fungi, they have also seen the birth of new big data technologies and analytical approaches to tackle these emerging pathogens. We review how the linked fields of genomics and epigenomics are transforming our ability to address the challenge of emerging fungal pathogens. We explore the methodologies and bioinformatic toolkits that currently exist to rapidly analyze the genomes of unknown fungi, then discuss how these data can be used to address key questions that shed light on their epidemiology...

The genomic era has been transformative for many fields, including our understanding of the phylogenetic relationships between organisms. The wide availability of whole-genome sequences practically eliminated data availability as a limiting factor for inferring phylogenetic trees, providing hundreds to thousands of loci for analyses, leading to molecular phylogenetics gradually being replaced by phylogenomics. The new era has also brought new challenges: systematic errors (resulting from, e.g., model violation) can be more pronounced in phylogenomic datasets and can lead to strongly supported incorrect relationships, creating significant incongruence among studies...

In the past decade, advances in next-generation sequencing technologies and bioinformatic pipelines for phylogenomic analysis have led to remarkable progress in fungal systematics and taxonomy. A number of long-standing questions have been addressed using comparative analysis of genome sequence data, resulting in robust multigene phylogenies. These have added to, and often surpassed traditional morphology or single-gene phylogenetic methods. In this chapter, we provide a brief history of fungal systematics and highlight some examples to demonstrate the impact of phylogenomics on this field...

Rust fungi (Pucciniales) are the most speciose and the most complex group of plant pathogens. Historically, rust taxonomy was largely influenced by host and phenotypic characters, which are potentially plastic. Molecular systematic studies suggest that the extant diversity of this group was largely shaped by host jumps and subsequent shifts. However, it has been challenging to reconstruct the evolutionary history for the order, especially at deeper (family-level) nodes. Phylogenomics offer a potentially powerful tool to reconstruct the Pucciniales tree of life, although researchers working at this vanguard still face unprecedented challenges working with nonculturable organisms that possess some of the largest and most repetitive genomes now known in kingdom fungi...

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...

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...

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...

Since its original inception over 150 years ago by Darwin, we have made tremendous progress toward the reconstruction of the Tree of Life. In particular, the transition from analyzing datasets comprised of small numbers of loci to those comprised of hundreds of loci, if not entire genomes, has aided in resolving some of the most vexing of evolutionary problems while giving us a new perspective on biodiversity. Correspondingly, phylogenetic trees have taken a central role in fields that span ecology, conservation, and medicine...

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Our own species has a diurnal activity pattern and an average circadian period of 24.2h. Exact determination of circadian period requires expensive and intrusive protocols, and investigators are therefore using chronotype questionnaires as a proxy quantitative measure. Both measures show a normal distribution suggestive of a polygenic trait. The genetic components of the 24-h feedback loop that generates circadian rhythms within our cells have been mapped in detail, identifying a number of candidate genes which have been investigated for genetic polymorphisms relating to the phenotypic variance...

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...

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...

Mitochondria are intracellular organelles responsible for adenosine triphosphate production. The strict control of intracellular energy needs require proper mitochondrial functioning. The mitochondria are under dual controls of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mitochondrial dysfunction can arise from changes in either mtDNA or nDNA genes regulating function. There are an estimated ∼1500 proteins in the mitoproteome, whereas the mtDNA genome has 37 proteins. There are, to date, ∼275 genes shown to give rise to disease...

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...

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 ABC protein superfamily-also called traffic ATPases-are energy-dependent ubiquitous proteins, representing one of the crucial and the largest family in the fungal genomes. The ATP-binding cassette endows a characteristic 200-250 amino acids and is omnipresent in all organisms ranging from prokaryotes to eukaryotes. Unlike in bacteria with nutrient import functions, ABC transporters in fungal entomopathogens serve as effective efflux pumps that are largely involved in the shuttle of metabolites across the biological membranes...

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...

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...

The genetics toolkit is pretty successful in drilling down into minutiae. The big challenge is to integrate the information from this specialty as well as those of biochemistry, physiology, behavior, and anatomy to explain how fundamental biological processes really work. Sleep, the circadian clock and development all qualify as overarching processes that encompass levels from molecule to behavior as part of their known mechanisms. They overlap each other, such that understanding the mechanisms of one can lead to insights into one of the others...

The filamentous fungus Neurospora crassa possesses a process called meiotic silencing by unpaired DNA (MSUD). MSUD has a remarkable ability to scan homologous chromosomes for unpaired DNA during meiosis. After unpaired DNA is identified, MSUD silences all RNA from the unpaired DNA along with any RNA transcribed from homologous sequences at other locations in the genome, regardless of their pairing state. The mechanism by which unpaired DNA is detected is unknown. Unpaired DNA segments can be as short as 1.3kb, if not shorter, and DNA sequences with only a small level of polymorphism (6%) can be considered unpaired by MSUD...