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Genes, Volume 10, Issue 4 (April 2019)

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Cover Story (view full-size image) Lupins are legumes that are diverse and geographically widespread mainly around Mediterranean basin [...] Read more.
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Open AccessReview
Modulation and Evolution of Animal Development through microRNA Regulation of Gene Expression
Received: 5 March 2019 / Revised: 20 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
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Abstract
microRNAs regulate gene expression by blocking the translation of mRNAs and/or promoting their degradation. They, therefore, play important roles in gene regulatory networks (GRNs) by modulating the expression levels of specific genes and can tune GRN outputs more broadly as part of feedback [...] Read more.
microRNAs regulate gene expression by blocking the translation of mRNAs and/or promoting their degradation. They, therefore, play important roles in gene regulatory networks (GRNs) by modulating the expression levels of specific genes and can tune GRN outputs more broadly as part of feedback loops. These roles for microRNAs provide developmental buffering on one hand but can facilitate evolution of development on the other. Here we review how microRNAs can modulate GRNs during animal development as part of feedback loops and through their individual or combinatorial targeting of multiple different genes in the same network. We then explore how changes in the expression of microRNAs and consequently targets can facilitate changes in GRNs that alter development and lead to phenotypic evolution. The reviewed studies exemplify the key roles played by microRNAs in the regulation and evolution of gene expression during developmental processes in animals. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Gene Expression)
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Open AccessArticle
Novel Y Chromosome Retrocopies in Canids Revealed through a Genome-Wide Association Study for Sex
Received: 25 March 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 25 April 2019
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Abstract
The lack of an annotated reference sequence for the canine Y chromosome has limited evolutionary studies, as well as our understanding of the role of Y-linked sequences in phenotypes with a sex bias. In genome-wide association studies (GWASs), we observed spurious associations with [...] Read more.
The lack of an annotated reference sequence for the canine Y chromosome has limited evolutionary studies, as well as our understanding of the role of Y-linked sequences in phenotypes with a sex bias. In genome-wide association studies (GWASs), we observed spurious associations with autosomal SNPs when sex was unbalanced in case-control cohorts and hypothesized that a subset of SNPs mapped to autosomes are in fact sex-linked. Using the Illumina 230K CanineHD array in a GWAS for sex, we identified SNPs that amplify in both sexes but possess significant allele frequency differences between males and females. We found 48 SNPs mapping to 14 regions of eight autosomes and the X chromosome that are Y-linked, appearing heterozygous in males and monomorphic in females. Within these 14 regions are eight genes: three autosomal and five X-linked. We investigated the autosomal genes (MITF, PPP2CB, and WNK1) and determined that the SNPs are diverged nucleotides in retrocopies that have transposed to the Y chromosome. MITFY and WNK1Y are expressed and appeared recently in the Canidae lineage, whereas PPP2CBY represents a much older insertion with no evidence of expression in the dog. This work reveals novel canid Y chromosome sequences and provides evidence for gene transposition to the Y from autosomes and the X. Full article
(This article belongs to the Special Issue Canine Genetics)
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Open AccessArticle
MicroRNAs Mediated Regulation of Expression of Nucleoside Analog Pathway Genes in Acute Myeloid Leukemia
Received: 26 March 2019 / Revised: 16 April 2019 / Accepted: 20 April 2019 / Published: 24 April 2019
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Abstract
Nucleoside analog, cytarabine (ara-C) is the mainstay of acute myeloid leukemia (AML) chemotherapy. Cytarabine and other nucleoside analogs require activation to the triphosphate form (ara-CTP). Intracellular ara-CTP levels demonstrate significant inter-patient variation and have been related to therapeutic response in AML patients. Inter-patient [...] Read more.
Nucleoside analog, cytarabine (ara-C) is the mainstay of acute myeloid leukemia (AML) chemotherapy. Cytarabine and other nucleoside analogs require activation to the triphosphate form (ara-CTP). Intracellular ara-CTP levels demonstrate significant inter-patient variation and have been related to therapeutic response in AML patients. Inter-patient variation in expression levels of drug transporters or enzymes involved in the activation or inactivation of cytarabine and other analogs is a prime mechanism contributing to development of drug resistance. Since microRNAs (miRNAs) are known to regulate gene-expression, the aim of this study was to identify miRNAs involved in regulation of messenger RNA expression levels of cytarabine pathway genes. We evaluated miRNA and gene-expression levels of cytarabine metabolic pathway genes in 8 AML cell lines and The Cancer Genome Atlas (TCGA) data base. Using correlation analysis and functional validation experiments, our data demonstrates that miR-34a-5p and miR-24-3p regulate DCK, an enzyme involved in activation of cytarabine and DCTD, an enzyme involved in metabolic inactivation of cytarabine expression, respectively. Further our results from gel shift assays confirmed binding of these mRNA-miRNA pairs. Our results show miRNA mediated regulation of gene expression levels of nucleoside metabolic pathway genes can impact interindividual variation in expression levels which in turn may influence treatment outcomes. Full article
(This article belongs to the Special Issue Pharmacogenomics and Personalized Medicine)
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Open AccessReview
The Response to DNA Damage at Telomeric Repeats and Its Consequences for Telomere Function
Received: 26 March 2019 / Revised: 13 April 2019 / Accepted: 18 April 2019 / Published: 24 April 2019
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Abstract
Telomeric repeats, coated by the shelterin complex, prevent inappropriate activation of the DNA damage response at the ends of linear chromosomes. Shelterin has evolved distinct solutions to protect telomeres from different aspects of the DNA damage response. These solutions include formation of t-loops, [...] Read more.
Telomeric repeats, coated by the shelterin complex, prevent inappropriate activation of the DNA damage response at the ends of linear chromosomes. Shelterin has evolved distinct solutions to protect telomeres from different aspects of the DNA damage response. These solutions include formation of t-loops, which can sequester the chromosome terminus from DNA-end sensors and inhibition of key steps in the DNA damage response. While blocking the DNA damage response at chromosome ends, telomeres make wide use of many of its players to deal with exogenous damage and replication stress. This review focuses on the interplay between the end-protection functions and the response to DNA damage occurring inside the telomeric repeats, as well as on the consequences that telomere damage has on telomere structure and function. Full article
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
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Open AccessArticle
Mitochondrial Introgression, Color Pattern Variation, and Severe Demographic Bottlenecks in Three Species of Malagasy Poison Frogs, Genus Mantella
Received: 6 February 2019 / Revised: 9 April 2019 / Accepted: 15 April 2019 / Published: 23 April 2019
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Abstract
Madagascar is a biodiversity hotspot particularly rich in amphibian diversity and only a few charismatic Malagasy amphibians have been investigated for their population-level differentiation. The Mantella madagascariensis group is composed of two rainforest and three swamp forest species of poison frogs. We first [...] Read more.
Madagascar is a biodiversity hotspot particularly rich in amphibian diversity and only a few charismatic Malagasy amphibians have been investigated for their population-level differentiation. The Mantella madagascariensis group is composed of two rainforest and three swamp forest species of poison frogs. We first confirm the monophyly of this clade using DNA sequences of three nuclear and four mitochondrial genes, and subsequently investigate the population genetic differentiation and demography of the swamp forest species using one mitochondrial, two nuclear and a set of nine microsatellite markers. Our results confirm the occurrence of two main mitochondrial lineages, one dominated by Mantella aurantiaca (a grouping supported also by our microsatellite-based tree) and the other by Mantella crocea + Mantella milotympanum. These two main lineages probably reflect an older divergence in swamp Mantella. Widespread mitochondrial introgression suggests a fairly common occurrence of inter-lineage gene flow. However, nuclear admixture seems to play only a limited role in this group, and the analyses of the RAG-1 marker points to a predominant incomplete lineage sorting scenario between all five species of the group, which probably diverged relatively recently. Our demographic analyses show a common, severe and recent demographic contraction, inferred to be in temporal coincidence with the massive deforestation events that took place in the past 1000 years. Current data do not allow to conclusively delimit independent evolutionary units in these frogs, and we therefore refrain to suggest any taxonomic changes. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reptiles and Amphibians)
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Open AccessArticle
Transcriptome Dynamics of Double Recessive Mutant, o2o2o16o16, Reveals the Transcriptional Mechanisms in the Increase of Its Lysine and Tryptophan Content in Maize
Received: 19 February 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 23 April 2019
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Abstract
In maize, pyramiding of o2 and o16 alleles can greatly improve the nutritional quality of grains. To dissect its molecular mechanism, we created a double recessive mutant line, o2o2o16o16, by introgression of the o2 and o16 alleles into the wild-type maize inbred [...] Read more.
In maize, pyramiding of o2 and o16 alleles can greatly improve the nutritional quality of grains. To dissect its molecular mechanism, we created a double recessive mutant line, o2o2o16o16, by introgression of the o2 and o16 alleles into the wild-type maize inbred line, by molecular marker-assisted backcross selection. The kernels (18 day after pollination (DAP), 28 DAP, and 38 DAP) of the o2o2o16o16 mutant and its parent lines were subject to RNA sequencing (RNA-Seq). The RNA-Seq analysis revealed that 59 differentially expressed genes (DEGs) were involved in lysine metabolism and 43 DEGs were involved in tryptophan metabolism. Among them, the genes encoding AK, ASADH, and Dap-F in the lysine synthesis pathway were upregulated at different stages of endosperm development, promoting the synthesis of lysine. Meanwhile, the genes encoding LKR/SDH and L-PO in the lysine degradation pathway were downregulated, inhibiting the degradation of lysine. Moreover, the genes encoding TAA and YUC in the tryptophan metabolic pathway were downregulated, restraining the degradation of tryptophan. Thus, pyramiding o2 and o16 alleles could increase the lysine and tryptophan content in maize. These above results would help to uncover the molecular mechanisms involved in the increase in lysine and the tryptophan content, through the introgression of o2 and o16 alleles into the wild-type maize. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle
The Biochemical Role of the Human NEIL1 and NEIL3 DNA Glycosylases on Model DNA Replication Forks
Received: 11 March 2019 / Revised: 15 April 2019 / Accepted: 17 April 2019 / Published: 23 April 2019
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Abstract
Endonuclease VIII-like (NEIL) 1 and 3 proteins eliminate oxidative DNA base damage and psoralen DNA interstrand crosslinks through initiation of base excision repair. Current evidence points to a DNA replication associated repair function of NEIL1 and NEIL3, correlating with induced expression of the [...] Read more.
Endonuclease VIII-like (NEIL) 1 and 3 proteins eliminate oxidative DNA base damage and psoralen DNA interstrand crosslinks through initiation of base excision repair. Current evidence points to a DNA replication associated repair function of NEIL1 and NEIL3, correlating with induced expression of the proteins in S/G2 phases of the cell cycle. However previous attempts to express and purify recombinant human NEIL3 in an active form have been challenging. In this study, both human NEIL1 and NEIL3 have been expressed and purified from E. coli, and the DNA glycosylase activity of these two proteins confirmed using single- and double-stranded DNA oligonucleotide substrates containing the oxidative bases, 5-hydroxyuracil, 8-oxoguanine and thymine glycol. To determine the biochemical role that NEIL1 and NEIL3 play during DNA replication, model replication fork substrates were designed containing the oxidized bases at one of three specific sites relative to the fork. Results indicate that whilst specificity for 5- hydroxyuracil and thymine glycol was observed, NEIL1 acts preferentially on double-stranded DNA, including the damage upstream to the replication fork, whereas NEIL3 preferentially excises oxidized bases from single stranded DNA and within open fork structures. Thus, NEIL1 and NEIL3 act in concert to remove oxidized bases from the replication fork. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
Systematic Identification and Evolution Analysis of Sox Genes in Coturnix japonica Based on Comparative Genomics
Received: 15 February 2019 / Revised: 16 April 2019 / Accepted: 20 April 2019 / Published: 22 April 2019
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Abstract
Coturnix japonica (Japanese quail) has been extensively used as a model animal for biological studies. The Sox gene family, which was systematically characterized by a high-mobility group (HMG-box) in many animal species, encodes transcription factors that play central roles during multiple developmental processes. [...] Read more.
Coturnix japonica (Japanese quail) has been extensively used as a model animal for biological studies. The Sox gene family, which was systematically characterized by a high-mobility group (HMG-box) in many animal species, encodes transcription factors that play central roles during multiple developmental processes. However, genome-wide investigations on the Sox gene family in birds are scarce. In the current study, we first performed a genome-wide study to explore the Sox gene family in galliform birds. Based on available genomic sequences retrieved from the NCBI database, we focused on the global identification of the Sox gene family in C. japonica and other species in Galliformes, and the evolutionary relationships of Sox genes. In our result, a total of 35 Sox genes in seven groups were identified in the C. japonica genome. Our results also revealed that dispersed gene duplications contributed the most to the expansion of the Sox gene family in Galliform birds. Evolutionary analyses indicated that Sox genes are an ancient gene family, and strong purifying selections played key roles in the evolution of CjSox genes of C. japonica. More interestingly, we observed that most Sox genes exhibited highly embryo-specific expression in both gonads. Our findings provided new insights into the molecular function and phylogeny of Sox gene family in birds. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessArticle
miR-194 Accelerates Apoptosis of Aβ1–42-Transduced Hippocampal Neurons by Inhibiting Nrn1 and Decreasing PI3K/Akt Signaling Pathway Activity
Received: 23 January 2019 / Revised: 8 April 2019 / Accepted: 10 April 2019 / Published: 21 April 2019
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Abstract
This article explores the mechanism of miR-194 on the proliferation and apoptosis of Aβ1–42-transduced hippocampal neurons. Aβ1–42-transduced hippocampal neuron model was established by inducing hippocampal neurons with Aβ1–42. MTT assay and flow cytometry were used to detect [...] Read more.
This article explores the mechanism of miR-194 on the proliferation and apoptosis of Aβ1–42-transduced hippocampal neurons. Aβ1–42-transduced hippocampal neuron model was established by inducing hippocampal neurons with Aβ1–42. MTT assay and flow cytometry were used to detect the viability and apoptosis of hippocampal neurons, respectively. qRT-PCR was used to detect changes in miR-194 and Nrn1 expression after Aβ1–42 induction. Aβ1–42-transduced hippocampal neurons were transfected with miR-194 mimics and/or Nrn1 overexpression vectors. Their viability and neurite length were detected by MTT assay and immunofluorescence, respectively. Western blot was used to detect protein expression. Aβ1–42 inhibited Aβ1–42-transduced hippocampal neuron activity and promoted their apoptosis in a dose-dependent manner. miR-194 was upregulated and Nrn1 was downregulated in Aβ1–42-transduced hippocampal neurons (p < 0.05). Compared with the model group, Aβ1–42-transduced hippocampal neurons of the miR-194 mimic group had much lower activity, average longest neurite length, Nrn1, p-AkT, and Bcl-2 protein expression and had much higher Bax, Caspase-3, and Cleaved Caspase-3 protein expression. Compared with the model group, Aβ1–42-transduced hippocampal neurons of the LV-Nrn1 group had much higher activity, average longest neurite length, Nrn1, p-AkT, and Bcl-2 protein expression and had much lower Bax, Caspase-3, and Cleaved Caspase-3 protein expression. Nrn1 is a target gene of miR-194. miR-194 inhibited apoptosis of Aβ1–42-transduced hippocampal neurons by inhibiting Nrn1 and decreasing PI3K/AkT signaling pathway activity. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
Novel Molecular Signatures in the PIP4K/PIP5K Family of Proteins Specific for Different Isozymes and Subfamilies Provide Important Insights into the Evolutionary Divergence of this Protein Family
Received: 22 February 2019 / Revised: 10 April 2019 / Accepted: 15 April 2019 / Published: 21 April 2019
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Abstract
Members of the PIP4K/PIP5K family of proteins, which generate the highly important secondary messenger phosphatidylinositol-4,5-bisphosphate, play central roles in regulating diverse signaling pathways. In eukaryotic organisms, multiple isozymes and subfamilies of PIP4K/PIP5K proteins are found and it is of much interest to understand [...] Read more.
Members of the PIP4K/PIP5K family of proteins, which generate the highly important secondary messenger phosphatidylinositol-4,5-bisphosphate, play central roles in regulating diverse signaling pathways. In eukaryotic organisms, multiple isozymes and subfamilies of PIP4K/PIP5K proteins are found and it is of much interest to understand their evolution and species distribution and what unique molecular and biochemical characteristics distinguish specific isozymes and subfamilies of proteins. We report here the species distribution of different PIP4K/PIP5K family of proteins in eukaryotic organisms and phylogenetic analysis based on their protein sequences. Our results indicate that the distinct homologs of both PIP4K and PIP5K are found in different organisms belonging to the Holozoa clade of eukaryotes, which comprises of various metazoan phyla as well as their close unicellular relatives Choanoflagellates and Filasterea. In contrast, the deeper-branching eukaryotic lineages, as well as plants and fungi, contain only a single homolog of the PIP4K/PIP5K proteins. In parallel, our comparative analyses of PIP4K/PIP5K protein sequences have identified six highly-specific molecular markers consisting of conserved signature indels (CSIs) that are uniquely shared by either the PIP4K or PIP5K proteins, or both, or specific subfamilies of these proteins. Of these molecular markers, 2 CSIs are distinctive characteristics of all PIP4K homologs, 1 CSI distinguishes the PIP4K and PIP5K homologs from the Holozoa clade of species from the ancestral form of PIP4K/PIP5K found in deeper-branching eukaryotic lineages. The remaining three CSIs are specific for the PIP5Kα, PIP5Kβ, and PIP4Kγ subfamilies of proteins from vertebrate species. These molecular markers provide important means for distinguishing different PIP4K/PIP5K isozymes as well as some of their subfamilies. In addition, the distribution patterns of these markers in different isozymes provide important insights into the evolutionary divergence of PIP4K/PIP5K proteins. Our results support the view that the Holozoa clade of eukaryotic organisms shared a common ancestor exclusive of the other eukaryotic lineages and that the initial gene duplication event leading to the divergence of distinct types of PIP4K and PIP5K homologs occurred in a common ancestor of this clade. Based on the results gleaned from different studies presented here, a model for the evolutionary divergence of the PIP4K/PIP5K family of proteins is presented. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
A Novel Aquaporin 12-like Protein from Chilo suppressalis: Characterization and Functional Analysis
Received: 20 February 2019 / Revised: 15 April 2019 / Accepted: 16 April 2019 / Published: 21 April 2019
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Abstract
Aquaporins (AQPs), which are members of the major intrinsic protein (MIP) family, play an important role in the transport of water and other small, uncharged solutes across membranes. In this study, we identified gene encoding two aquaporin 12-like (AQP12L) proteins, CsAqp12L_v1 and CsAqp12L_v2 [...] Read more.
Aquaporins (AQPs), which are members of the major intrinsic protein (MIP) family, play an important role in the transport of water and other small, uncharged solutes across membranes. In this study, we identified gene encoding two aquaporin 12-like (AQP12L) proteins, CsAqp12L_v1 and CsAqp12L_v2, from Chilo suppressalis, a serious rice pest in Asia. Phylogenetic analysis indicated that CsAQP12L_V1 and CsAQP12L_V2 were grouped in a well-supported cluster that included other members of Lepidoptera. The two proteins are almost identical, except that CsAQP12L_V1 lacks 34 amino acids that are present in CsAQP12L_V2 at site 217. The qRT-PCR indicated that both CsAqp12L and CsAqp12L_v2 were expressed in heads, epidermis, foregut, midgut, and hindguts, with the highest level of expression in hindguts, heads, and epidermis. Expression of CsAqp12L and CsAqp12L_v2 was detected in all life stages and both sexes and was highest in first instar larvae and lowest in eggs. Expression of CsAqp12L and CsAqp12L_v2 was not significantly altered by exposure to brief changes in temperature. There were no significant differences in the third instar larvae, male and female pupae, and female adults in response to adverse humidity. However, the mRNA level of CsAqp12L in the fifth instar larvae and CsAqp12L_v2 in male adults was induced significantly by low humidity, respectively. Moreover, Xenopus oocytes injected with cRNAs of CsAQP12L_V1 and CsAQP12L_V2 showed no significant changes in permeability to water, glycerol, trehalose, or urea. The two CsAQP12L variants likely localize to an intracellular location in C. suppressalis and may respond to novel stimuli. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessReview
The Elaboration of miRNA Regulation and Gene Regulatory Networks in Plant–Microbe Interactions
Received: 27 February 2019 / Revised: 3 April 2019 / Accepted: 12 April 2019 / Published: 21 April 2019
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Abstract
Plants are exposed to diverse abiotic and biotic stimuli. These require fast and specific integrated responses. Such responses are coordinated at the protein and transcript levels and are incorporated into larger regulatory networks. Here, we focus on the evolution of transcriptional regulatory networks [...] Read more.
Plants are exposed to diverse abiotic and biotic stimuli. These require fast and specific integrated responses. Such responses are coordinated at the protein and transcript levels and are incorporated into larger regulatory networks. Here, we focus on the evolution of transcriptional regulatory networks involved in plant–pathogen interactions. We discuss the evolution of regulatory networks and their role in fine-tuning plant defense responses. Based on the observation that many of the cornerstones of immune signaling in angiosperms are also present in streptophyte algae, it is likely that some regulatory components also predate the origin of land plants. The degree of functional conservation of many of these ancient components has not been elucidated. However, ongoing functional analyses in bryophytes show that some components are conserved. Hence, some of these regulatory components and how they are wired may also trace back to the last common ancestor of land plants or earlier. Of course, an understanding of the similarities and differences during the evolution of plant defense networks cannot ignore the lineage-specific coevolution between plants and their pathogens. In this review, we specifically focus on the small RNA regulatory networks involved in fine-tuning of the strength and timing of defense responses and highlight examples of pathogen exploitation of the host RNA silencing system. These examples illustrate well how pathogens frequently target gene regulation and thereby alter immune responses on a larger scale. That this is effective is demonstrated by the diversity of pathogens from distinct kingdoms capable of manipulating the same gene regulatory networks, such as the RNA silencing machinery. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Gene Expression)
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Open AccessArticle
Genomic Features, Comparative Genomic Analysis, and Antimicrobial Susceptibility Patterns of Chryseobacterium arthrosphaerae Strain ED882-96 Isolated in Taiwan
Received: 18 March 2019 / Revised: 5 April 2019 / Accepted: 18 April 2019 / Published: 20 April 2019
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Abstract
Bacteria belonging to the genus Chryseobacterium are ubiquitously distributed in natural environments, plants, and animals. Except C. indologenes and C. gleum, other Chryseobacterium species rarely cause human diseases. This study reported the whole-genome features, comparative genomic analysis, and antimicrobial susceptibility patterns of [...] Read more.
Bacteria belonging to the genus Chryseobacterium are ubiquitously distributed in natural environments, plants, and animals. Except C. indologenes and C. gleum, other Chryseobacterium species rarely cause human diseases. This study reported the whole-genome features, comparative genomic analysis, and antimicrobial susceptibility patterns of C. arthrosphaerae ED882-96 isolated in Taiwan. Strain ED882-96 was collected from the blood of a patient who had alcoholic liver cirrhosis and was an intravenous drug abuser. This isolate was initially identified as C. indologenes by using matrix-assisted laser desorption ionization–time of flight mass spectrometry. The analysis of 16S ribosomal RNA gene sequence revealed that ED882-96 shared 100% sequence identity with C. arthrosphaerae type strain CC-VM-7T. The results of whole-genome sequencing of ED882-96 showed two chromosome contigs and one plasmid. The total lengths of the draft genomes of chromosome and plasmid were 4,249,864 bp and 435,667 bp, respectively. The findings of both in silico DNA–DNA hybridization and average nucleotide identity analyses clearly demonstrated that strain ED882-96 was a species of C. arthrosphaerae. A total of 83 potential virulence factor homologs were predicted in the whole-genome sequencing of strain ED882-96. This isolate was resistant to all tested antibiotics, including β-lactams, β-lactam/β-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, tetracycline, glycylcycline, and trimethoprim-sulfamethoxazole. Only one antibiotic resistance gene was recognized in the plasmid. By contrast, many antibiotic resistance genes were identified in the chromosome. The findings of this study suggest that strain ED882-96 is a highly virulent and multidrug-resistant pathogen. Knowledge regarding genomic characteristics and antimicrobial susceptibility patterns provides valuable insights into this uncommon species. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessOpinion
Allele Frequency Difference AFD–An Intuitive Alternative to FST for Quantifying Genetic Population Differentiation
Received: 21 February 2019 / Revised: 8 April 2019 / Accepted: 12 April 2019 / Published: 18 April 2019
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Abstract
Measuring the magnitude of differentiation between populations based on genetic markers is commonplace in ecology, evolution, and conservation biology. The predominant differentiation metric used for this purpose is FST. Based on a qualitative survey, numerical analyses, simulations, and empirical data, I [...] Read more.
Measuring the magnitude of differentiation between populations based on genetic markers is commonplace in ecology, evolution, and conservation biology. The predominant differentiation metric used for this purpose is FST. Based on a qualitative survey, numerical analyses, simulations, and empirical data, I here argue that FST does not express the relationship to allele frequency differentiation between populations generally considered interpretable and desirable by researchers. In particular, FST (1) has low sensitivity when population differentiation is weak, (2) is contingent on the minor allele frequency across the populations, (3) can be strongly affected by asymmetry in sample sizes, and (4) can differ greatly among the available estimators. Together, these features can complicate pattern recognition and interpretation in population genetic and genomic analysis, as illustrated by empirical examples, and overall compromise the comparability of population differentiation among markers and study systems. I argue that a simple differentiation metric displaying intuitive properties, the absolute allele frequency difference AFD, provides a valuable alternative to FST. I provide a general definition of AFD applicable to both bi- and multi-allelic markers and conclude by making recommendations on the sample sizes needed to achieve robust differentiation estimates using AFD. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessArticle
EcoTILLING Reveals Natural Allelic Variations in Starch Synthesis Key Gene TaSSIV and Its Haplotypes Associated with Higher Thousand Grain Weight
Received: 18 February 2019 / Revised: 5 April 2019 / Accepted: 8 April 2019 / Published: 18 April 2019
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Abstract
Wheat is a staple food commodity grown worldwide, and wheat starch is a valuable source of energy and carbon that constitutes 80% of the grain weight. Manipulation of genes involved in starch synthesis significantly affects wheat grain weight and yield. TaSSIV plays an [...] Read more.
Wheat is a staple food commodity grown worldwide, and wheat starch is a valuable source of energy and carbon that constitutes 80% of the grain weight. Manipulation of genes involved in starch synthesis significantly affects wheat grain weight and yield. TaSSIV plays an important role in starch synthesis and its main function is granule formation. To mine and stack more favorable alleles, single nucleotide polymorphisms (SNPs) of TaSSIV-A, B, and D were investigated across 362 wheat accessions by Ecotype-Targeting Induced Local Lesions IN Genome (EcoTILLING). As a result, a total of 38 SNPs in the amplified regions of three TaSSIV genes were identified, of which 10, 15, and 13 were in TaSSIV-A, B, and D, respectively. These 38 SNPs were evaluated by using KASP and six SNPs showed an allele frequency >5% whereas the rest were <5%, i.e., considered to be minor alleles. In the Chinese mini core collection, three haplotypes were detected for TaSSIV–A and three for TaSSIV–B. The results of an association study in the Chinese mini core collection with thousand grain weight (TGW) and spike length (SPL) showed that Hap-2-1A was significantly associated with TGW and Hap-3-1B with SPL. Allelic frequency and geographic distribution indicated that the favored haplotype (Hap-2-1A) has been positively selected in Chinese wheat breeding. These results suggested that the Kompetitive Allele Specific PCR (KASP) markers can be applied in starch improvement to ultimately improve wheat yield by marker assisted selection in wheat breeding. Full article
(This article belongs to the Special Issue TILLING and CRISPR to design the varieties of tomorrow)
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Open AccessArticle
Shedding Light on a Secretive Tertiary Urodelean Relict: Hynobiid Salamanders (Paradactylodon persicus s.l.) from Iran, Illuminated by Phylogeographic, Developmental, and Transcriptomic Data
Received: 17 March 2019 / Revised: 10 April 2019 / Accepted: 11 April 2019 / Published: 18 April 2019
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Abstract
The Hyrcanian Forests present a unique Tertiary relict ecosystem, covering the northern Elburz and Talysh Ranges (Iran, Azerbaijan), a poorly investigated, unique biodiversity hotspot with many cryptic species. Since the 1970s, two nominal species of Urodela, Hynobiidae, Batrachuperus (later: Paradactylodon) have been [...] Read more.
The Hyrcanian Forests present a unique Tertiary relict ecosystem, covering the northern Elburz and Talysh Ranges (Iran, Azerbaijan), a poorly investigated, unique biodiversity hotspot with many cryptic species. Since the 1970s, two nominal species of Urodela, Hynobiidae, Batrachuperus (later: Paradactylodon) have been described: Paradactylodon persicus from northwestern and P. gorganensis from northeastern Iran. Although P. gorganensis has been involved in studies on phylogeny and development, there is little data on the phylogeography, systematics, and development of the genus throughout the Hyrcanian Forests; genome-wide resources have been entirely missing. Given the huge genome size of hynobiids, making whole genome sequencing hardly affordable, we aimed to publish the first transcriptomic resources for Paradactylodon from an embryo and a larva (9.17 Gb RNA sequences; assembled to 78,918 unigenes). We also listed 32 genes involved in vertebrate sexual development and sex determination. Photographic documentation of the development from egg sacs across several embryonal and larval stages until metamorphosis enabled, for the first time, comparison of the ontogeny with that of other hynobiids and new histological and transcriptomic insights into early gonads and timing of their differentiation. Transcriptomes from central Elburz, next-generation sequencing (NGS) libraries of archival DNA of topotypic P. persicus, and GenBank-sequences of eastern P. gorganensis allowed phylogenetic analysis with three mitochondrial genomes, supplemented by PCR-amplified mtDNA-fragments from 17 museum specimens, documenting <2% uncorrected intraspecific genetic distance. Our data suggest that these rare salamanders belong to a single species P. persicus s.l. Humankind has a great responsibility to protect this species and the unique biodiversity of the Hyrcanian Forest ecosystems. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reptiles and Amphibians)
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Open AccessArticle
Identification of Transcription Factors Involved in the Regulation of Flowering in Adonis Amurensis Through Combined RNA-seq Transcriptomics and iTRAQ Proteomics
Received: 6 March 2019 / Revised: 7 April 2019 / Accepted: 15 April 2019 / Published: 18 April 2019
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Abstract
Temperature is one of the most important environmental factors affecting flowering in plants. Adonis amurensis, a perennial herbaceous flower that blooms in early spring in northeast China where the temperature can drop to −15 °C, is an ideal model for studying the [...] Read more.
Temperature is one of the most important environmental factors affecting flowering in plants. Adonis amurensis, a perennial herbaceous flower that blooms in early spring in northeast China where the temperature can drop to −15 °C, is an ideal model for studying the molecular mechanisms of flowering at extremely low temperatures. This study first investigated global gene expression profiles at different developmental stages of flowering in A. amurensis by RNA-seq transcriptome and iTRAQ proteomics. Finally, 123 transcription factors (TFs) were detected in both the transcriptome and the proteome. Of these, 66 TFs belonging to 14 families may play a key role in multiple signaling pathways of flowering in A. amurensis. The TFs FAR1, PHD, and B3 may be involved in responses to light and temperature, while SCL, SWI/SNF, ARF, and ERF may be involved in the regulation of hormone balance. SPL may regulate the age pathway. Some members of the TCP, ZFP, MYB, WRKY, and bHLH families may be involved in the transcriptional regulation of flowering genes. The MADS-box TFs are the key regulators of flowering in A. amurensis. Our results provide a direction for understanding the molecular mechanisms of flowering in A. amurensis at low temperatures. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle
DNA Barcode Reveals the Bycatch of Endangered Batoids Species in the Southwest Atlantic: Implications for Sustainable Fisheries Management and Conservation Efforts
Received: 26 February 2019 / Revised: 1 April 2019 / Accepted: 1 April 2019 / Published: 18 April 2019
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Abstract
Today, elasmobranchs are one the most threatened vertebrate groups worldwide. In fact, at least 90% of elasmobranch species are listed in the International Union for Conservation of Nature (IUCN) Red List, while more than 40% are data-deficient. Although these vertebrates are mainly affected [...] Read more.
Today, elasmobranchs are one the most threatened vertebrate groups worldwide. In fact, at least 90% of elasmobranch species are listed in the International Union for Conservation of Nature (IUCN) Red List, while more than 40% are data-deficient. Although these vertebrates are mainly affected by unsustainable fishery activities, bycatch is also one of the major threats to sharks and batoids worldwide, and represents a challenge for both sustainable fishery management and for biodiversity and conservational efforts. Thus, in this study, DNA barcode methodology was used to identify the bycatch composition of batoid species from small-scale industrial fisheries in the southwest Atlantic and artisanal fisheries from southeast Brazil. A total of 228 individuals belonging to four Chondrichthyes orders, seven families, and at least 17 distinct batoid species were sequenced; among these individuals, 131 belonged to species protected in Brazil, 101 to globally threatened species, and some to species with trade restrictions provided by Appendix II of the Convention on International Trade in Endangered Species (CITES). These results highlight the impacts on marine biodiversity of bycatch by small-scale industrial and unmanaged artisanal fisheries from the southwest Atlantic, and support the implementation of DNA-based methodologies for species-specific identification in data-poor fisheries as a powerful tool for improving the quality of fisheries’ catch statistics and for keeping precise bycatch records. Full article
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Open AccessArticle
Identification and Characterization of Salt-Responsive MicroRNAs in Vicia faba by High-Throughput Sequencing
Received: 10 March 2019 / Revised: 2 April 2019 / Accepted: 11 April 2019 / Published: 17 April 2019
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Abstract
Salt stress has detrimental effects on plant growth and development. MicroRNAs (miRNAs) are a class of noncoding RNAs that are involved in post-transcriptional gene expression regulation. In this study, small RNA sequencing was employed to identify the salt stress-responsive miRNAs of the salt-sensitive [...] Read more.
Salt stress has detrimental effects on plant growth and development. MicroRNAs (miRNAs) are a class of noncoding RNAs that are involved in post-transcriptional gene expression regulation. In this study, small RNA sequencing was employed to identify the salt stress-responsive miRNAs of the salt-sensitive Hassawi-3 and the salt-tolerant ILB4347 genotypes of faba bean, growing under salt stress. A total of 527 miRNAs in Hassawi-3 plants, and 693 miRNAs in ILB4347 plants, were found to be differentially expressed. Additionally, 284 upregulated and 243 downregulated miRNAs in Hassawi-3, and 298 upregulated and 395 downregulated miRNAs in ILB4347 plants growing in control and stress conditions were recorded. Target prediction and annotation revealed that these miRNAs regulate specific salt-responsive genes, which primarily included genes encoding transcription factors and laccases, superoxide dismutase, plantacyanin, and F-box proteins. The salt-responsive miRNAs and their targets were functionally enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, which showed that the miRNAs were involved in salt stress-related biological pathways, including the ABC transporter pathway, MAPK signaling pathway, plant hormone signal transduction, and the phosphatidylinositol signaling system, among others, suggesting that the miRNAs play an important role in the salt stress tolerance of the ILB4347 genotype. These results offer a novel understanding of the regulatory role of miRNAs in the salt response of the salt-tolerant ILB4347 and the salt-sensitive Hassawi-3 faba bean genotypes. Full article
(This article belongs to the Special Issue Plant miRNA Mediated Defense Response)
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Open AccessTechnical Note
Development and Validation of Sex-Specific Markers in Pelodiscus Sinensis Using Restriction Site-Associated DNA Sequencing
Received: 7 March 2019 / Revised: 3 April 2019 / Accepted: 10 April 2019 / Published: 15 April 2019
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Abstract
The sex of an animal influences its economic traits, especially in species displaying sexual dimorphism. The Chinese soft-shelled turtle, Pelodiscus sinensis, is an economically important aquatic species that shows significant male sexual dimorphism, with a large body size, faster growth, a thick [...] Read more.
The sex of an animal influences its economic traits, especially in species displaying sexual dimorphism. The Chinese soft-shelled turtle, Pelodiscus sinensis, is an economically important aquatic species that shows significant male sexual dimorphism, with a large body size, faster growth, a thick and wide calipash, and lower body fat. In this study, ten male and ten female turtles were subjected to restriction site-associated DNA sequencing (RAD-seq) using the Hi-Seq 4000 sequencing platform to isolate female-specific DNA fragments. We identified 5967 bp and 6532 bp fragments using genome walking. Three female-specific markers designed from these two fragments were confirmed to separate the sexes of Pelodiscus sinensis perfectly. One of the female-specific markers showed dosage association in female and male individuals. Individuals from different populations (n = 296) were used to validate that the female-specific markers could identify the genetic sex of Pelodiscus sinensis with 100% accuracy. The results of the present study demonstrated that RAD-seq was useful to develop sex-related markers in animals, and verified that the sex determination system of Pelodiscus sinensis belonged to the ZZ/ZW heterogametic system. Importantly, the developed markers could lead to a method for sex-controlled breeding in the Chinese soft-shelled turtle. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reptiles and Amphibians)
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Open AccessArticle
The Genome of Blue-Capped Cordon-Bleu Uncovers Hidden Diversity of LTR Retrotransposons in Zebra Finch
Received: 6 March 2019 / Revised: 5 April 2019 / Accepted: 5 April 2019 / Published: 13 April 2019
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Abstract
Avian genomes have perplexed researchers by being conservative in both size and rearrangements, while simultaneously holding the blueprints for a massive species radiation during the last 65 million years (My). Transposable elements (TEs) in bird genomes are relatively scarce but have been implicated [...] Read more.
Avian genomes have perplexed researchers by being conservative in both size and rearrangements, while simultaneously holding the blueprints for a massive species radiation during the last 65 million years (My). Transposable elements (TEs) in bird genomes are relatively scarce but have been implicated as important hotspots for chromosomal inversions. In zebra finch (Taeniopygia guttata), long terminal repeat (LTR) retrotransposons have proliferated and are positively associated with chromosomal breakpoint regions. Here, we present the genome, karyotype and transposons of blue-capped cordon-bleu (Uraeginthus cyanocephalus), an African songbird that diverged from zebra finch at the root of estrildid finches 10 million years ago (Mya). This constitutes the third linked-read sequenced genome assembly and fourth in-depth curated TE library of any bird. Exploration of TE diversity on this brief evolutionary timescale constitutes a considerable increase in resolution for avian TE biology and allowed us to uncover 4.5 Mb more LTR retrotransposons in the zebra finch genome. In blue-capped cordon-bleu, we likewise observed a recent LTR accumulation indicating that this is a shared feature of Estrildidae. Curiously, we discovered 25 new endogenous retrovirus-like LTR retrotransposon families of which at least 21 are present in zebra finch but were previously undiscovered. This highlights the importance of studying close relatives of model organisms. Full article
(This article belongs to the Special Issue Repetitive DNA Sequences)
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Open AccessArticle
Molecular Characterization of a Dirofilaria immitis Cysteine Protease Inhibitor (Cystatin) and Its Possible Role in Filarial Immune Evasion
Received: 17 February 2019 / Revised: 7 April 2019 / Accepted: 8 April 2019 / Published: 12 April 2019
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Abstract
Infection with canine heartworm (Dirofilaria immitis), spread via mosquito vectors, causes coughing, asthma, pneumonia, and bronchitis in humans and other animals. The disease is especially severe and often fatal in dogs and represents a serious threat to public health worldwide. Cysteine [...] Read more.
Infection with canine heartworm (Dirofilaria immitis), spread via mosquito vectors, causes coughing, asthma, pneumonia, and bronchitis in humans and other animals. The disease is especially severe and often fatal in dogs and represents a serious threat to public health worldwide. Cysteine protease inhibitors (CPIs), also known as cystatins, are major immunomodulators of the host immune response during nematode infections. Herein, we cloned and expressed the cystatin Di-CPI from D. immitis. Sequence analysis revealed two specific cystatin-like domains, a Q-x-V-x-G motif, and a SND motif. Phylogenetic analysis indicates that Di-CPI is a member of the second subgroup of nematode type II cystatins. Probing of D. immitis total proteins with anti-rDi-CPI polyclonal antibody revealed a weak signal, and immunofluorescence-based histochemical analysis showed that native Di-CPI is mainly localized in the cuticle of male and female worms and the gut of male worms. Treatment of canine peripheral blood mononuclear cells (PMBCs) with recombinant Di-CPI induced a Th2-type immune response characterized by high expression of the anti-inflammatory factor interleukin-10. Proliferation assays showed that Di-CPI inhibits the proliferation of canine PMBCs by 15%. Together, the results indicate that Di-CPI might be related to cellular hyporesponsiveness in dirofilariasis and may help D. immitis to evade the host immune system. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle
Commensal and Pathogenic Members of the Dental Calculus Microbiome of Badia Pozzeveri Individuals from the 11th to 19th Centuries
Received: 1 February 2019 / Revised: 3 April 2019 / Accepted: 5 April 2019 / Published: 12 April 2019
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Abstract
The concept of the human oral microbiome was applied to understand health and disease, lifestyles, and dietary habits throughout part of human history. In the present study, we augment the understanding of ancient oral microbiomes by characterizing human dental calculus samples recovered from [...] Read more.
The concept of the human oral microbiome was applied to understand health and disease, lifestyles, and dietary habits throughout part of human history. In the present study, we augment the understanding of ancient oral microbiomes by characterizing human dental calculus samples recovered from the ancient Abbey of Badia Pozzeveri (central Italy), with differences in socioeconomic status, time period, burial type, and sex. Samples dating from the Middle Ages (11th century) to the Industrial Revolution era (19th century) were characterized using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene V4 region. Consistent with previous studies, individuals from Badia Pozzeveri possessed commensal oral bacteria that resembled modern oral microbiomes. These results suggest that members of the oral microbiome are ubiquitous despite differences in geographical regions, time period, sex, and socioeconomic status. The presence of fecal bacteria could be in agreement with poor hygiene practices, consistent with the time period. Respiratory tract, nosocomial, and other rare pathogens detected in the dental calculus samples are intriguing and could suggest subject-specific comorbidities that could be reflected in the oral microbiome. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle
Computational Methods for Detection of Differentially Methylated Regions Using Kernel Distance and Scan Statistics
Received: 28 February 2019 / Revised: 29 March 2019 / Accepted: 8 April 2019 / Published: 12 April 2019
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Abstract
Motivation: Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation because they play an important role in regulating gene expression without changes in the sequence of DNA. Abnormal DNA methylation is associated with many human diseases. Results: We propose [...] Read more.
Motivation: Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation because they play an important role in regulating gene expression without changes in the sequence of DNA. Abnormal DNA methylation is associated with many human diseases. Results: We propose two different approaches to test for differentially methylated regions (DMRs) associated with complex traits, while accounting for correlations among CpG sites in the DMRs. The first approach is a nonparametric method using a kernel distance statistic and the second one is a likelihood-based method using a binomial spatial scan statistic. The kernel distance method uses the kernel function, while the binomial scan statistic approach uses a mixed-effects model to incorporate correlations among CpG sites. Extensive simulations show that both approaches have excellent control of type I error, and both have reasonable statistical power. The binomial scan statistic approach appears to have higher power, while the kernel distance method is computationally faster. The proposed methods are demonstrated using data from a chronic lymphocytic leukemia (CLL) study. Full article
(This article belongs to the Special Issue Bioinformatic Analysis for Rare Diseases)
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Open AccessArticle
Tracking Biodistribution of Myeloid-Derived Cells in Murine Models of Breast Cancer
Received: 21 February 2019 / Revised: 29 March 2019 / Accepted: 3 April 2019 / Published: 12 April 2019
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Abstract
A growing tumor is constantly secreting inflammatory chemokines and cytokines that induce release of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and macrophages, from the bone marrow. These cells not only promote tumor growth, but also prepare distant organs for tumor metastasis. [...] Read more.
A growing tumor is constantly secreting inflammatory chemokines and cytokines that induce release of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and macrophages, from the bone marrow. These cells not only promote tumor growth, but also prepare distant organs for tumor metastasis. On the other hand, the myeloid-derived cells also have phagocytic potential, and can serve as vehicles for drug delivery. We have previously identified thioaptamers that bind a subset of MDSCs with high affinity and specificity. In the current study, we applied one of the thioaptamers as a probe to track myeloid cell distribution in the bone, liver, spleen and tumor in multiple murine models of breast cancer including the 4T1 syngeneic model and MDA-MB-231 and SUM159 xenograft models. Information generated from this study will facilitate further understanding of tumor growth and metastasis, and predict biodistribution patterns of cell-mediated drug delivery. Full article
(This article belongs to the Special Issue DNA Origami and Aptamer Assemblies)
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Open AccessArticle
The Alternative Splicing Landscape of Brassica napus Infected with Leptosphaeria maculans
Received: 2 March 2019 / Revised: 10 April 2019 / Accepted: 10 April 2019 / Published: 11 April 2019
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Abstract
Alternative splicing (AS) is a post-transcriptional regulatory process that enhances transcriptome diversity, thereby affecting plant growth, development, and stress responses. To identify the new transcripts and changes in the isoform-level AS landscape of rapeseed (Brassica napus) infected with the fungal pathogen [...] Read more.
Alternative splicing (AS) is a post-transcriptional regulatory process that enhances transcriptome diversity, thereby affecting plant growth, development, and stress responses. To identify the new transcripts and changes in the isoform-level AS landscape of rapeseed (Brassica napus) infected with the fungal pathogen Leptosphaeria maculans, we compared eight RNA-seq libraries prepared from mock-inoculated and inoculated B. napus cotyledons and stems. The AS events that occurred in stems were almost the same as those in cotyledons, with intron retention representing the most common AS pattern. We identified 1892 differentially spliced genes between inoculated and uninoculated plants. We performed a weighted gene co-expression network analysis (WGCNA) to identify eight co-expression modules and their Hub genes, which are the genes most connected with other genes within each module. There are nine Hub genes, encoding nine transcription factors, which represent key regulators of each module, including members of the NAC, WRKY, TRAF, AP2/ERF-ERF, C2H2, C2C2-GATA, HMG, bHLH, and C2C2-CO-like families. Finally, 52 and 117 alternatively spliced genes in cotyledons and stems were also differentially expressed between mock-infected and infected materials, such as HMG and C2C2-Dof; which have dual regulatory mechanisms in response to L. maculans. The splicing of the candidate genes identified in this study could be exploited to improve resistance to L. maculans. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessReview
A Systematically Assembled Signature of Genes to be Deep-Sequenced for Their Associations with the Blood Pressure Response to Exercise
Received: 9 March 2019 / Revised: 4 April 2019 / Accepted: 4 April 2019 / Published: 11 April 2019
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Abstract
Background: Exercise is one of the best nonpharmacologic therapies to treat hypertension. The blood pressure (BP) response to exercise is heritable. Yet, the genetic basis for the antihypertensive effects of exercise remains elusive. Methods: To assemble a prioritized gene signature, we performed [...] Read more.
Background: Exercise is one of the best nonpharmacologic therapies to treat hypertension. The blood pressure (BP) response to exercise is heritable. Yet, the genetic basis for the antihypertensive effects of exercise remains elusive. Methods: To assemble a prioritized gene signature, we performed a systematic review with a series of Boolean searches in PubMed (including Medline) from earliest coverage. The inclusion criteria were human genes in major BP regulatory pathways reported to be associated with: (1) the BP response to exercise; (2) hypertension in genome-wide association studies (GWAS); (3) the BP response to pharmacotherapy; (4a) physical activity and/or obesity in GWAS; and (4b) BP, physical activity, and/or obesity in non-GWAS. Included GWAS reports disclosed the statistically significant thresholds used for multiple testing. Results: The search yielded 1422 reports. Of these, 57 trials qualified from which we extracted 11 genes under criteria 1, 18 genes under criteria 2, 28 genes under criteria 3, 27 genes under criteria 4a, and 29 genes under criteria 4b. We also included 41 genes identified from our previous work. Conclusions: Deep-sequencing the exons of this systematically assembled signature of genes represents a cost and time efficient approach to investigate the genomic basis for the antihypertensive effects of exercise. Full article
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Open AccessArticle
ORTHOSCOPE Analysis Reveals the Presence of the Cellulose Synthase Gene in All Tunicate Genomes but Not in Other Animal Genomes
Received: 8 March 2019 / Revised: 3 April 2019 / Accepted: 5 April 2019 / Published: 10 April 2019
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Abstract
Tunicates or urochordates—comprising ascidians, larvaceans, and salps—are the only metazoans that can synthesize cellulose, a biological function usually associated with bacteria and plants but not animals. Tunicate cellulose or tunicine is a major component of the outer acellular coverage (tunic) of the entire [...] Read more.
Tunicates or urochordates—comprising ascidians, larvaceans, and salps—are the only metazoans that can synthesize cellulose, a biological function usually associated with bacteria and plants but not animals. Tunicate cellulose or tunicine is a major component of the outer acellular coverage (tunic) of the entire body of these organisms. Previous studies have suggested that the prokaryotic cellulose synthase gene (CesA) was horizontally transferred into the genome of a tunicate ancestor. However, no convenient tools have been devised to determine whether only tunicates harbor CesA. ORTHOSCOPE is a recently developed tool used to identify orthologous genes and to examine the phylogenic relationship of molecules within major metazoan taxa. The present analysis with this tool revealed the presence of CesA orthologs in all sequenced tunicate genomes but an absence in other metazoan genomes. This supports an evolutionary origin of animal cellulose and provides insights into the evolution of this animal taxon. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessArticle
Bayes Factor-Based Regulatory Gene Network Analysis of Genome-Wide Association Study of Economic Traits in a Purebred Swine Population
Received: 3 February 2019 / Revised: 8 March 2019 / Accepted: 1 April 2019 / Published: 10 April 2019
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Abstract
Early stage prediction of economic trait performance is important and directly linked to profitability of farm pig production. Genome-wide association study (GWAS) has been applied to find causative genomic regions of traits. This study established a regulatory gene network using GWAS for critical [...] Read more.
Early stage prediction of economic trait performance is important and directly linked to profitability of farm pig production. Genome-wide association study (GWAS) has been applied to find causative genomic regions of traits. This study established a regulatory gene network using GWAS for critical economic pig characteristics, centered on easily measurable body fat thickness in live animals. We genotyped 2,681 pigs using Illumina Porcine SNP60, followed by GWAS to calculate Bayes factors for 47,697 single nucleotide polymorphisms (SNPs) of seven traits. Using this information, SNPs were annotated with specific genes near genome locations to establish the association weight matrix. The entire network consisted of 226 nodes and 6,921 significant edges. For in silico validation of their interactions, we conducted regulatory sequence analysis of predicted target genes of transcription factors (TFs). Three key regulatory TFs were identified to guarantee maximum coverage: AT-rich interaction domain 3B (ARID3B), glial cell missing homolog 1 (GCM1), and GLI family zinc finger 2 (GLI2). We identified numerous genes targeted by ARID3B, associated with cellular processes. GCM1 and GLI2 were involved in developmental processes, and their shared target genes regulated multicellular organismal process. This system biology-based function analysis might contribute to enhancing understanding of economic pig traits. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessArticle
Going Deeper into High and Low Phylogenetic Relationships of Protura
Received: 16 March 2019 / Revised: 3 April 2019 / Accepted: 5 April 2019 / Published: 10 April 2019
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Abstract
Proturans are small, wingless, soil-dwelling arthropods, generally associated with the early diversification of Hexapoda. Their bizarre morphology, together with conflicting results of molecular studies, has nevertheless made their classification ambiguous. Furthermore, their limited dispersal capability (due to the primarily absence of wings) and [...] Read more.
Proturans are small, wingless, soil-dwelling arthropods, generally associated with the early diversification of Hexapoda. Their bizarre morphology, together with conflicting results of molecular studies, has nevertheless made their classification ambiguous. Furthermore, their limited dispersal capability (due to the primarily absence of wings) and their euedaphic lifestyle have greatly complicated species-level identification. Mitochondrial and nuclear markers have been applied herein to investigate and summarize proturan systematics at different hierarchical levels. Two new mitochondrial genomes are described and included in a phylum-level phylogenetic analysis, but the position of Protura could not be resolved with confidence due to an accelerated rate of substitution and extensive gene rearrangements. Mitochondrial and nuclear loci were also applied in order to revise the intra-class systematics, recovering three proturan orders and most of the families/subfamilies included as monophyletic, with the exception of the subfamily Acerentominae. At the species level, most morphologically described species were confirmed using molecular markers, with some exceptions, and the advantages of including nuclear, as well as mitochondrial, markers and morphology are discussed. At all levels, an enlarged taxon sampling and the integration of data from different sources may be of significant help in solving open questions that still persist on the evolutionary history of Protura. Full article
(This article belongs to the Special Issue Tools for Population and Evolutionary Genetics)
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