Genes 2019-2020 Best Cover Award Survey

Cover 1: How epigenetic Modifications (Mods) of small RNAs facilitate adaptation and the way back to homeostasis. This occurs all the way from bacteria (black bacilli from our gut loosing their pili) to humans (blue fellows raising their hands).
Full text is free to access: https://www.mdpi.com/2073-4425/10/1/22

Cover 2: Observations of chemo/radio-resistant cells undergoing reversible polyploidy presented in this issue by Salmina et al. in the article “The cancer aneuploidy paradox: In the light of evolution” address this paradox. Through a dysfunctional spindle, cancer stem cells segregate parental groups of end-to-end linked dyads originating tetraploid cells. This is followed by autokaryogamy, pairing and recombination at centromeres in the octoploid endo-prophase. The process is completed by reduction divisions and release of secondary cells. It shares features with asexual ploidy cycles seen earlier in evolution, facilitating a reduction in the mutational load of aneuploidy. The image shows a polyploid endometaphase of a lymphoma cell on day 7 post 10 Gy irradiation which displays 16 chromosomes #18 as revealed by tri-colour FISH (short arm, green; centre red; long arm terminus blue).
Full text is free to access: https://www.mdpi.com/2073-4425/10/2/83

Cover 3: The unexpected lysis of a 1 m3 culture of Halobacterium salinarum strain S9 was found to be caused by a novel caudovirus, pictured in the right panel of the diagram. We named it ChaoS9, partly because of the damage it had caused, and sequenced its 55,145 bp dsDNA genome. The closest relatives were found to be the myohaloviruses phiH1 and phiCh1, both of which infect extremely halophilic archaea (Class Halobacteria). Strong conservation of the tail genes contrasts with major differences of the head genes. Even more surprising is the similarity of the major capsid protein with that of tailed halovirus HHTV-1. Presumably, the evolutionary history of ChaoS9 exemplifies widespread recombination between tailed haloviruses. Another curious feature are many, closely matching CRISPR spacers to ChaoS9 in metagenomic data from hypersaline Antarctic lakes.
Full text is free to access: https://www.mdpi.com/2073-4425/10/3/194

Cover 4: Lupins are legumes that are diverse and geographically widespread mainly around Mediterranean basin and both Americas. European lupins also exhibit great variability in chromosome number (2n=32-52), the basic chromosome number (x=5-9, 13) and genome size (0.97 pg/2C to 2.44 pg/2C). Comparative BAC-FISH analyses highlighted chromosomes variations and its multiple rearrangements. We proposed along with phylogeny data, the model of lupin chromosome evolution through three round of whole genome duplication, with assistance to aneuploidy. We assume the basic chromosome number as x=6, that is considered also for American lupins. The outstanding complex genome evolution makes lupin fascinating model for evolutionary studies. Polyploidy may provide an privilege in domestication, thus development of fundamental (cyto)genetic is a crucial to utilisate lupins in modern plant improvement.
Full text is free to access: https://www.mdpi.com/2073-4425/10/4/259

Cover 5: Domestic dog, Canis lupus familiaris, breeds each have a distinct standard for their morphological appearance, with the coat being particularly prominent. In each breed, this consists of either a double or single layer of hair. Two single nucleotide changes within a regulatory region are suggestive causative variants, resulting in single coats within the dog lineage. Pictured is the Shetland Sheepdog, which is known for its lush double coat. Image courtesy of Dr. Dayna Dreger.
Full text is free to access: https://www.mdpi.com/2073-4425/10/5/323

Cover 6: Pet dogs are potentially the most powerful natural model for many human diseases, including cancer, autoimmune disorders and psychiatric diseases (Image courtesy of Trish McMillan). In this issue, Megquier et al introduce the Barkbase data portal, a new epigenomic resource for dog research. Barkbase catalogs functional genomic regions in dozens of tissues from six adult dogs, who differed in ancestry, age, and size, as well as from embryos at four developmental time points. Modeled on similar resources in human genomics, this new portal supports efforts to identify and investigate canine genetic variants associated with traits and diseases. All data is freely accessible at barkbase.org with additional data in production.
Full text is free to access: https://www.mdpi.com/2073-4425/10/6/433

Cover 7: The human gut microbiota, that means the types of organisms that are present in an environmental habitat, consisting of trillions of microbial cells and thousands of bacterial species and it encompasses ~10−13 microorganisms. A growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases and, in turn, they are influenced by environment and nutritional behaviors. One of the most popular diets is the very low carbohydrate aka ketogenic diet. (KD). The KD is used for different aims: from weight loss to neurological diseases but its impact on microbiota is still poorly investigated but we know that ketones (produced during a KD) have positive effects on gut’s health. We investigated the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.
Full text is free to access: https://www.mdpi.com/2073-4425/10/7/534
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Cover 8: We investigated the mechanisms explaining the colonisation of Cantabrian sky islands (Spain) in an endemic flightless grasshopper (Chorthippus cazurroi). We evaluated the fitting of two migration models to understand the extant genetic structure in these populations: long-distance dispersal (LDD) and gradual distance dispersal (GDD). We found that GDD fits the real data better than LDD model, with an onset of the expansion matching with postglacial expansions after the retreat of the ice sheets. The gradual expansion process along the Cantabrian sky islands found here seems to be conditioned by the suitability of habitats and the presence of alpine corridors. Our findings shed light on our understanding about how organisms adapted to live in alpine habitats with limited dispersal abilities have faced new and suitable environmental conditions.
Full text is free to access: https://www.mdpi.com/2073-4425/10/8/590

Cover 9: Long considered incurable, inherited retinal diseases (IRDs) are currently at the forefront of the development of novel therapeutic strategies. Many of these strategies focus on resolving the primary cause of the disease, a mutation in one of the many genes associated with IRD. This group of therapeutic strategies, coined ‘molecular therapies’ can act at the DNA, RNA or protein level, and all aim to improve visual function, or at least slow down or halt disease progression, following administration to the retina. Which of the strategies will be most useful for each patient depends on many factors, including the type of genetic defect, its prevalence, target gene and cell type, delivery methods, and the state of the disease at the possible time of intervention. The different approaches, as well as the many factors that need to be taken into account, are summarized in this review.
Full text is free to access: https://www.mdpi.com/2073-4425/10/9/654

Cover 10: Development is orchestrated by regulatory elements that turn genes ON or OFF in precise patterns. Many safety mechanisms prevent a regulatory element from inappropriately regulating the wrong gene. In flies and mammals, dedicated DNA elements called insulators recruit insulator binding proteins (IBPs) to shield promoters from regulatory elements. A single IBP called CCCTC-binding factor (CTCF) is known in mammals, whereas functional studies in Drosophila have identified several IBPs. How insulators function at the molecular level is unclear, but they may fold chromosomes into conformations that affect regulatory element-promoter communication. We compare and contrast recent studies in flies and mice to ask: Is insulation important for animal development? Though requirements for insulation differ, insulation emerges as a conserved and critical gene regulation strategy.
Full text is free to access: https://www.mdpi.com/2073-4425/10/10/767

Cover 11: Globally, we find ourselves in the midst of a biodiversity crisis and in need of conservation tools to help preserve the species that remain. Advances in sequencing technologies and reduction in sequencing costs have given rise to the era of genomics. Whole-genome data can provide answers to a variety of crucial conservation questions including understanding demography and population structure, minimising inbreeding, maximising adaptive potential, and identifying the basis of important phenotypic traits. Incorporation of genomic data to assist in the recovery of threatened species is vital; however, it is often unclear how reference genomes facilitate the use of genomics in management practice. In this review we use the Tasmanian devil as a model to demonstrate specific examples of how a reference genome can aid management actions in the conservation of threatened species.
Full text is free to access: https://www.mdpi.com/2073-4425/10/11/846

Cover 12: Acute myeloid leukemia (AML) clinical settings cannot do without molecular testing to confirm or rule out predictive biomarkers for prognostic stratification, in order to initiate or withhold targeted therapy. In this context, we present a nanopore-based assay for rapid (24 hours) sequencing of six genes (NPM1, FLT3, CEBPA, TP53, IDH1, and IDH2) that are recurrently mutated in AML. Nanopore ability to generate long reads allows a more accurate detection of longer FLT3 internal tandem duplications and phasing double CEBPA mutations. The workflow proposed can potentially enable all basic molecular biology laboratories to perform detailed targeted gene sequencing analysis in AML patients, in order to define the prognosis and the treatment.
Full text is free to access: https://www.mdpi.com/2073-4425/10/12/1026

Cover 13: Astronaut Dr. Peggy Whitson turns the maintenance work area (MWA, blue surface) into a research bench aboard the International Space Station (ISS). Enabled by the miniPCR (Amplyus) and the MinION (Oxford Nanopore Technologies), pictured side-by-side on the MWA, Whitson prepared and sequenced DNA from bacteria collected from, and cultured aboard, the ISS. The agar slide used for bacterial culture was returned to the ground for standard laboratory processing and identification. The identifications obtained aboard the ISS matched those determined on the ground down to the species level, marking the first ever identification of microbes entirely off Earth.
Full text is free to access: https://www.mdpi.com/2073-4425/11/1/76

Cover 14: Populations that are asymmetrically isolated, such as above waterfalls, can sometimes export emigrants in a direction from which they do not receive immigrants, and thus provide an excellent opportunity to study the evolution of dispersal traits. We investigated the rheotaxis of guppies above barrier waterfalls in the Aripo and Turure rivers in Trinidad—the later having been introduced in 1957 from a below-waterfall population in another drainage. We predicted that, as a result of strong selection against downstream emigration, both of these above-waterfall populations should show strong positive rheotaxis. Matching these expectations, both populations expressed high levels of positive rheotaxis, possibly reflecting contemporary (rapid) evolution in the introduced Turure population.
Full text is free to access: https://www.mdpi.com/2073-4425/11/2/180

Cover 15: DNA helicases are motor enzymes that move directionally along the phosphodiester backbone to catalyze ATP-dependent unwinding of duplex DNA. The discovery of viral, prokaryotic, and eukaryotic DNA helicases since the 1970s indicates their ubiquitous presence. DNA helicases have fundamentally important roles in virtually all aspects of nucleic acid metabolism including DNA replication and repair, recombination, transcription, and maintenance of genomic stability. Research by many laboratories has elucidated their molecular and cellular functions. Genetic defects in DNA helicases underlie hereditary diseases and cancers. Continued work in this area is anticipated to yield important new insights to the seminal importance of DNA helicases in genome biology.
Full text is free to access: https://www.mdpi.com/2073-4425/11/3/255

Cover 16: Flowers can have different symmetry plans: bilateral, like the orchid Phalaenopsis equestris, asymmetric, like Strelitzia reginae, or radial, like Zinnia elegans. Many transcription factors are involved in the establishment of floral symmetry. During plant evolution, the MYB transcription factors DIVARICATA, RADIALIS, and DRIF have acquired the ability to interact with each other, forming the DDR module. This regulatory module has a pivotal role in determining which kind of floral symmetry is established.
Full text is free to access: https://www.mdpi.com/2073-4425/11/4/395

Cover 17: Llamas are invaluable genetic resources of Peru. They are pack animals, and their fiber is used for clothing. Despite their importance, their population is decreasing. In this context, the Camelid Germplasm Bank—Quimsachata shelters a collection of llamas from their two phenotypes, Ch'aku and Q'ara, from different regions of Peru. Assessing the genetic variability and differentiation of the llama population from the Germplasm Bank, a high genetic variation was found among individuals, hence evidencing an adequate genetic management to conserve and maintain llama diversity.
Full text is free to access: https://www.mdpi.com/2073-4425/11/5/541

Cover 18: Making a mistake when trying to generate a new CRISPR mouse model can waste thousands of dollars and result in months of lost time. Using mouse blastocysts, we describe, step by step, a fast, reliable, and inexpensive method for testing CRISPR components prior to their use in engineering mice. We discovered that a DNA donor sequence complementary to the guide appeared to be incorporated earlier in development than a same-sense donor. We also found that when donors contained silent mutations about every 10 bp between the cut site and desired mutation, increasing the distance between the two no longer reduced successful donor sequence incorporation.
Full text is free to access: https://www.mdpi.com/2073-4425/11/6/628

Cover 19: Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. We summarize the sterol biosynthesis, transport and detoxification systems of S. cerevisiae, as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of ERG genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.
Full text is free to access: https://www.mdpi.com/2073-4425/11/7/795

Cover 20: Structures of TORC1, the GTPases and related factors that control TORC1, and TORC2 have expanded our understanding of the regulation of the highly conserved TOR signaling pathway and potentiate development of clinically-relevant strategies to manipulate it.
Full text is free to access: https://www.mdpi.com/2073-4425/11/8/885

Cover 21: The beetle–fungus symbioses of drugstore and cigarette beetles with their symbiont Symbiotaphrina are a forgotten system of animal–fungus interactions. Several features make them unique research organisms, including 1) the symbiont is both extracellular and intracellular during the life cycle of the host, and 2) both beetle and fungus can be cultured in isolation. Fungal symbionts intracellularly infect cells in the larval and adult beetle gut, while accessory glands in adult females harbor extracellular fungi that are passed to the next generation. Modern methods provide incredible opportunities for these systems to emerge as model organisms for research spanning the microbiota, pathogenesis/infection, and mutualism.
Full text is free to access: https://www.mdpi.com/2073-4425/11/9/1063

Cover 22: Adaptation to changing environment is a growing challenge in the era of the “Anthropocene”, and populations capable of rapid adaptation to novel selection pressures are more likely to survive. The Caspian whipsnake (Dolichophis caspius) is a large-bodied, non-venomous colubrid and inhabits dry steppe and Mediterranean habitats, from Eastern Europe around the Caspian and Black Sea to the north-western edge of its distribution in Hungary. Applying ddRAD sequencing we investigated genetic diversity and adaptive evolution to local habitat types and identified 751 selected genotypes correlated with seven key climatic variables. We found that isothermality may have an important role in the distribution and adaptation of Caspian whipsnakes.
Full text is free to access: https://www.mdpi.com/2073-4425/11/10/1218

Cover 23: To date, there is little evidence supporting a role of Y chromosome genetic variation in relation to human complex traits. This review summarises inherent complexities specific to the Y chromosome related to its structure, function and population history that make the human Y chromosome a complex locus, different from all other human chromosomes. We propose that this complexity needs to be taken into account in the design and interpretation of genetic epidemiological studies involving chromosome Y. In particular, we discuss evidence and propose novel ideas about the consideration of haplogroups in genetic association studies of the human Y chromosome and complex traits.
Full text is free to access: https://www.mdpi.com/2073-4425/11/11/1273

Cover 24: Multiple myeloma is a genetically heterogeneous disease, arising and progressing through the appearance and accumulation of a tangle of genomic aberrations. In the last decade, cheap and widely applicable sequencing technologies have allowed significant advantages in its biological knowledge. However, a divide between the enormous bulk of available preclinical data and the scalability of these data in the clinical setting still exists.
This review aims to focus on genomic events that drive plasma cell disorders, including their clinical significance according to evidence available from phase 3 randomized trials.
Full text is free to access: https://www.mdpi.com/2073-4425/11/12/1453

Genes 2019-2020 Best Cover Award

Question Title

Five cover stories will be chosen from the 2019 and 2020 cover stories and each of the owners will receive 200 CHF. The criteria that will be considered for selection are as follows: importance or innovation of the research; open to all career levels; quality of the cover image.