Genes

15 pages, 2071 KiB

Open AccessArticle

Fitness Costs of the Glutathione S-Transferase Epsilon 2 (L119F-GSTe2) Mediated Metabolic Resistance to Insecticides in the Major African Malaria Vector Anopheles Funestus

by Magellan Tchouakui^1,2,*

, Jacob M. Riveron^1,3, Doumani Djonabaye^1,4, Williams Tchapga¹

, Helen Irving³, Patrice Soh Takam⁵, Flobert Njiokou^1,2 and Charles S. Wondji^1,3,*

¹ LSTM Research Unit at the Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaoundé, Cameroon

² Parasitology and Ecology Laboratory, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812 Yaoundé, Cameroon

³ Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L35QA, UK

⁴ Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812 Yaoundé, Cameroon

⁵ Department of Mathematics, Faculty of Science, University of Yaoundé 1, P.O. Box 812 Yaoundé, Cameroon

Genes 2018, 9(12), 645; https://doi.org/10.3390/genes9120645 - 19 Dec 2018

Cited by 42 | Viewed by 4821

Abstract

Metabolic resistance to insecticides threatens malaria control. However, little is known about its fitness cost in field populations of malaria vectors, thus limiting the design of suitable resistance management strategies. Here, we assessed the association between the glutathione S-transferase GSTe2-mediated metabolic resistance [...] Read more.

Metabolic resistance to insecticides threatens malaria control. However, little is known about its fitness cost in field populations of malaria vectors, thus limiting the design of suitable resistance management strategies. Here, we assessed the association between the glutathione S-transferase GSTe2-mediated metabolic resistance and life-traits of natural populations of Anopheles funestus. A total of 1200 indoor resting blood-fed female An. funestus (F₀) were collected in Mibellon, Cameroon (2016/2017), and allowed to lay eggs individually. Genotyping of F1 mosquitoes for the L119F-GSTE2 mutation revealed that L/L119-homozygote susceptible (SS) mosquitoes significantly laid more eggs than heterozygotes L119F-RS (odds ratio (OR) = 2.06; p < 0.0001) and homozygote resistant 119F/F-RR (OR = 2.93; p < 0.0001). L/L119-SS susceptible mosquitoes also showed the higher ability for oviposition than 119F/F-RR resistant (OR = 2.68; p = 0.0002) indicating a reduced fecundity in resistant mosquitoes. Furthermore, L119F-RS larvae developed faster (nine days) than L119F-RR and L119F-SS (11 days) (X² = 11.052; degree of freedom (df) = 4; p = 0.02) suggesting a heterozygote advantage effect for larval development. Interestingly, L/L119-SS developed faster than 119F/F-RR (OR = 5.3; p < 0.0001) revealing an increased developmental time in resistant mosquitoes. However, genotyping and sequencing revealed that L119F-RR mosquitoes exhibited a higher adult longevity compared to RS (OR > 2.2; p < 0.05) and SS (OR > 2.1; p < 0.05) with an increased frequency of GSTe2-resistant haplotypes in mosquitoes of D30 after adult emergence. Additionally, comparison of the expression of GSTe2 revealed a significantly increased expression from D1-D30 after emergence of adults (Anova test (F) = 8; df= 3; p = 0.008). The negative association between GSTe2 and some life traits of An. funestus could facilitate new resistance management strategies. However, the increased longevity of GSTe2-resistant mosquitoes suggests that an increase in resistance could exacerbate malaria transmission. Full article

(This article belongs to the Special Issue Genetics of Insecticide Resistance)

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16 pages, 3126 KiB

Open AccessArticle

MafA Expression Preserves Immune Homeostasis in Human and Mouse Islets

by Tania Singh¹, Luis Sarmiento²

, Cheng Luan²

, Rashmi B. Prasad²

, Jenny Johansson¹, Luis R. Cataldo¹, Erik Renström², Shamit Soneji¹, Corrado Cilio² and Isabella Artner^1,2,*

¹ Stem Cell Center, Lund University, 22184 Lund, Sweden

² Lund University Diabetes Centre, 22184 Lund, Sweden

Genes 2018, 9(12), 644; https://doi.org/10.3390/genes9120644 - 18 Dec 2018

Cited by 9 | Viewed by 5509

Abstract

Type 1 (T1D) and type 2 (T2D) diabetes are triggered by a combination of environmental and/or genetic factors. Maf transcription factors regulate pancreatic beta (β)-cell function, and have also been implicated in the regulation of immunomodulatory cytokines like interferon-β (IFNβ1). In this study, [...] Read more.

Type 1 (T1D) and type 2 (T2D) diabetes are triggered by a combination of environmental and/or genetic factors. Maf transcription factors regulate pancreatic beta (β)-cell function, and have also been implicated in the regulation of immunomodulatory cytokines like interferon-β (IFNβ1). In this study, we assessed MAFA and MAFB co-expression with pro-inflammatory cytokine signaling genes in RNA-seq data from human pancreatic islets. Interestingly, MAFA expression was strongly negatively correlated with cytokine-induced signaling (such as IFNAR1, DDX58) and T1D susceptibility genes (IFIH1), whereas correlation of these genes with MAFB was weaker. In order to evaluate if the loss of MafA altered the immune status of islets, MafA deficient mouse islets (MafA^−/−) were assessed for inherent anti-viral response and susceptibility to enterovirus infection. MafA deficient mouse islets had elevated basal levels of Ifnβ1, Rig1 (DDX58 in humans), and Mda5 (IFIH1) which resulted in reduced virus propagation in response to coxsackievirus B3 (CVB3) infection. Moreover, an acute knockdown of MafA in β-cell lines also enhanced Rig1 and Mda5 protein levels. Our results suggest that precise regulation of MAFA levels is critical for islet cell-specific cytokine production, which is a critical parameter for the inflammatory status of pancreatic islets. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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9 pages, 2185 KiB

Open AccessArticle

Exploring the Variable Phenotypes of RPGR Carrier Females in Assessing Their Potential for Retinal Gene Therapy

by Anika Nanda^1,*, Anna P. Salvetti^1,2

, Penny Clouston³, Susan M. Downes¹ and Robert E. MacLaren^1,4

¹ Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK

² Eye Clinic, Sacco Hospital, University of Milan, 20157 Milan, Italy

³ Oxford Medical Genetics Laboratories, The Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, UK

⁴ Nuffield Department of Clinical Neurosciences, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK

Genes 2018, 9(12), 643; https://doi.org/10.3390/genes9120643 - 18 Dec 2018

Cited by 43 | Viewed by 5098

Abstract

Inherited retinal degenerations are the leading cause of blindness in the working population. X-linked retinitis pigmentosa (XLRP), caused by mutations in the Retinitis pigmentosa GTPase regulator (RPGR) gene is one of the more severe forms, and female carriers of RPGR mutations [...] Read more.

Inherited retinal degenerations are the leading cause of blindness in the working population. X-linked retinitis pigmentosa (XLRP), caused by mutations in the Retinitis pigmentosa GTPase regulator (RPGR) gene is one of the more severe forms, and female carriers of RPGR mutations have a variable presentation. A retrospective review of twenty-three female RPGR carriers aged between 8 and 76 years old was carried out using fundoscopy, autofluorescence imaging (AF), blue reflectance (BR) imaging and optical coherence tomography (OCT). Confirmation of the genetic mutation was obtained from male relatives or Sanger genetic sequencing. Fundus examination and AF demonstrate phenotypic variability in RPGR carriers. The genetic mutation appears indeterminate of the degree of change. We found four distinct classifications based on AF images to describe RPGR carriers; normal (N) representing normal or near-normal AF appearance (n = 1, 4%); radial (R) pattern reflex without pigmentary retinopathy (n = 14, 61%); focal (F) pigmentary retinopathy (n = 5, 22%) and; male (M) phenotype (n = 3, 13%). The phenotypes were precisely correlated in both eyes (rs = 1.0, p < 0.0001). Skewed X-inactivation can result in severely affected carrier females—in some cases indistinguishable from the male pattern and these patients should be considered for RPGR gene therapy. In the cases of the male (M) phenotype where the X-inactivation was skewed, the pattern was similar in both eyes, suggesting that the mechanism is not truly random but may have an underlying genetic basis. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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14 pages, 1503 KiB

Open AccessReview

Detection and Analysis of RNA Ribose 2′-O-Methylations: Challenges and Solutions

by Yuri Motorin^1,*

and Virginie Marchand²

¹ UMR7365 IMoPA, Biopôle, CNRS-Lorraine University, 9 Avenue de la Forêt de Haye, 54505 Vandoeuvre-les-Nancy, France

² UMS2008 IBSLor, Biopôle, CNRS-Lorraine University-INSERM, 9 Avenue de la Forêt de Haye, 54505 Vandoeuvre-les-Nancy, France

Genes 2018, 9(12), 642; https://doi.org/10.3390/genes9120642 - 18 Dec 2018

Cited by 48 | Viewed by 7920

Abstract

Ribose 2′-O-methylation is certainly one of the most common RNA modifications found in almost any type of cellular RNA. It decorates transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs) (and most probably small nucleolar RNAs, snoRNAs), as well as [...] Read more.

Ribose 2′-O-methylation is certainly one of the most common RNA modifications found in almost any type of cellular RNA. It decorates transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs) (and most probably small nucleolar RNAs, snoRNAs), as well as regulatory RNAs like microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), and finally, eukaryotic messenger RNAs (mRNAs). Due to this exceptional widespread of RNA 2′-O-methylation, considerable efforts were made in order to precisely map these numerous modifications. Extensive studies of RNA 2′-O-methylation were also stimulated by the discovery of C/D-box snoRNA-guided machinery, which insures site-specific modification of hundreds 2′-O-methylated residues in archaeal and eukaryotic rRNAs and some other RNAs. In this brief review we discussed both traditional approaches of RNA biochemistry and also modern deep sequencing-based methods, used for detection/mapping and quantification of RNA 2′-O-methylations. Full article

(This article belongs to the Special Issue RNA Modifications)

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15 pages, 1049 KiB

Open AccessArticle

Blood-Based Biomarkers for Predicting the Risk for Five-Year Incident Coronary Heart Disease in the Framingham Heart Study via Machine Learning

by Meeshanthini V. Dogan^1,2,3,*, Steven R. H. Beach⁴, Ronald L. Simons⁵, Amaury Lendasse^6,7, Brandan Penaluna⁸ and Robert A. Philibert^1,2,3,8

¹ Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA

² Cardio Diagnostics LLC, 2500 Crosspark Road, Coralville, IA 52241, USA

³ Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA

⁴ Department of Psychology, University of Georgia, Athens, GA 30602, USA

⁵ Department of Sociology, University of Georgia, Athens, GA 30606, USA

⁶ Information and Logistics Technology Department, University of Houston, Houston, TX 77004, USA

⁷ Department of Business Management and Analytics, Arcada University of Applied Sciences, 00560 Helsinki, Finland

⁸ Behavioral Diagnostics LLC, 2500 Crosspark Road, Coralville, IA 52241, USA

Genes 2018, 9(12), 641; https://doi.org/10.3390/genes9120641 - 18 Dec 2018

Cited by 34 | Viewed by 6988

Abstract

An improved approach for predicting the risk for incident coronary heart disease (CHD) could lead to substantial improvements in cardiovascular health. Previously, we have shown that genetic and epigenetic loci could predict CHD status more sensitively than conventional risk factors. Herein, we examine [...] Read more.

An improved approach for predicting the risk for incident coronary heart disease (CHD) could lead to substantial improvements in cardiovascular health. Previously, we have shown that genetic and epigenetic loci could predict CHD status more sensitively than conventional risk factors. Herein, we examine whether similar machine learning approaches could be used to develop a similar panel for predicting incident CHD. Training and test sets consisted of 1180 and 524 individuals, respectively. Data mining techniques were employed to mine for predictive biosignatures in the training set. An ensemble of Random Forest models consisting of four genetic and four epigenetic loci was trained on the training set and subsequently evaluated on the test set. The test sensitivity and specificity were 0.70 and 0.74, respectively. In contrast, the Framingham risk score and atherosclerotic cardiovascular disease (ASCVD) risk estimator performed with test sensitivities of 0.20 and 0.38, respectively. Notably, the integrated genetic-epigenetic model predicted risk better for both genders and very well in the three-year risk prediction window. We describe a novel DNA-based precision medicine tool capable of capturing the complex genetic and environmental relationships that contribute to the risk of CHD, and being mapped to actionable risk factors that may be leveraged to guide risk modification efforts. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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20 pages, 1329 KiB

Open AccessArticle

Fragmented Nuclear DNA Is the Predominant Genetic Material in Human Hair Shafts

by Michael D. Brandhagen^†, Odile Loreille^†

and Jodi A. Irwin^*

¹ DNA Support Unit, FBI Laboratory, 2501 Investigation Parkway, Quantico, VA 22135, USA

^† These authors contributed equally to this work.

Genes 2018, 9(12), 640; https://doi.org/10.3390/genes9120640 - 18 Dec 2018

Cited by 50 | Viewed by 9059

Abstract

While shed hairs are one of the most commonly encountered evidence types, they are among the most limited in terms of DNA quantity and quality. As a result, nuclear DNA short tandem repeat (STR) profiling is generally unsuccessful and DNA testing of shed [...] Read more.

While shed hairs are one of the most commonly encountered evidence types, they are among the most limited in terms of DNA quantity and quality. As a result, nuclear DNA short tandem repeat (STR) profiling is generally unsuccessful and DNA testing of shed hair is instead performed by targeting the mitochondrial DNA control region. Although the high copy number of mitochondrial DNA relative to nuclear DNA routinely permits the recovery of mitochondrial DNA (mtDNA) data in these cases, mtDNA profiles do not offer the discriminatory power of nuclear DNA profiles. In order to better understand the total content and degradation state of DNA in single shed hairs and assess the feasibility of recovering highly discriminatory nuclear DNA data from this common evidence type, high throughput shotgun sequencing was performed on both recently collected and aged (approximately 50-year-old) hair samples. The data reflect trends that have been demonstrated previously with other technologies, namely that mtDNA quantity and quality decrease along the length of the hair shaft. In addition, the shotgun data reveal that nuclear DNA is present in shed hair and surprisingly abundant relative to mitochondrial DNA, even in the most distal fragments. Nuclear DNA comprised, at minimum, 88% of the total human reads in any given sample, and generally more than 95%. Here, we characterize both the nuclear and mitochondrial DNA content of shed hairs and discuss the implications of these data for forensic investigations. Full article

(This article belongs to the Special Issue Forensic Genomics)

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22 pages, 7607 KiB

Open AccessArticle

De Novo Analysis Reveals Transcriptomic Responses in Eriobotrya japonica Fruits during Postharvest Cold Storage

by Shoukai Lin^1,2

, Ti Wu^3,4, Hailan Lin^1,3, Yanqing Zhang¹, Shichang Xu¹, Jinge Wang^1,5, Bisha Wu^1,2, Yu Chen^1,2, Suying Lin^1,2, Dahe Lin^1,2, Xiumei Wang¹, Xiaoxu Zhao² and Jincheng Wu^1,2,*

¹ Key Laboratory of Loquat Germplasm Innovation and Utilization (Putian University), Fujian Province University, Putian 351100, China

² Fujian Provincial Key Laboratory of Ecology-toxicological Effects & Control for Emerging Contaminants, Putian University, Putian 351100, China

³ Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada

⁴ Overseas Education College, Fujian Agriculture and Forestry University, Fuzhou 350002, China

⁵ College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Genes 2018, 9(12), 639; https://doi.org/10.3390/genes9120639 - 17 Dec 2018

Cited by 22 | Viewed by 4473

Abstract

Cold storage is the primary preservation method of postharvest loquat fruits. However, cold storage also results in many chilling injury physiological disorders called lignification, which decreases the quality and economic value of the fruits. Few studies to date have focused on the transcriptomic [...] Read more.

Cold storage is the primary preservation method of postharvest loquat fruits. However, cold storage also results in many chilling injury physiological disorders called lignification, which decreases the quality and economic value of the fruits. Few studies to date have focused on the transcriptomic responses associated with lignification except lignin synthesis pathways. This study aimed to explore the changes of loquat transcriptome during long-term cold storage. Our results showed that the gene expression patterns were differed among the five stages. The differentially expressed genes (DEGs) in response to cold storage were more intense and complex in earlier stage. The membrane-related genes preferentially responded to low temperature and were followed by intracellular-located genes. The cold-induced pathways were mainly concerned with signal transduction and secondary metabolism (i.e., lignin, pectin, cellulose, terpenoid, carotenoid, steroid) in the first three stages and were chiefly related to primary metabolism in the later two stages, especially energy metabolism. Further investigation suggested that 503 protein kinases, 106 protein phosphatases, and 40 Ca²⁺ signal components were involved in the cold signal transduction of postharvest loquat fruits. We predicted a pathway including 649 encoding genes of 49 enzymes, which displayed the metabolisms of major sugars and polysaccharides in cold-stored loquat fruits. The coordinated expression patterns of these genes might contribute to the changes of saccharides in the pathway. These results provide new insight into the transcriptomic changes of postharvest loquat fruits in response to cold storage environment, which may be helpful for improving the postharvest life of loquat in the future. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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12 pages, 3297 KiB

Open AccessArticle

The 5′-3′ Exoribonuclease XRN4 Regulates Auxin Response via the Degradation of Auxin Receptor Transcripts

by David Windels^1,2,* and Etienne Bucher^1,2

¹ Botanical Institute, University of Basel, Zurich-Basel Plant Science Center, Part of the Swiss Plant Science Web, Schönbeinstrasse 6, 4056 Basel, Switzerland

² IRHS, Agrocampus-Ouest, INRA, Université d’Angers, SFR 4207 QuaSaV, 49071 Beaucouzé, France

Genes 2018, 9(12), 638; https://doi.org/10.3390/genes9120638 - 17 Dec 2018

Cited by 7 | Viewed by 4329

Abstract

Auxin is a major hormone which plays crucial roles in instructing virtually all developmental programs of plants. Its signaling depends primarily on its perception by four partially redundant receptors of the TIR1/AFB2 clade (TAARs), which subsequently mediate the specific degradation of AUX/IAA transcriptional [...] Read more.

Auxin is a major hormone which plays crucial roles in instructing virtually all developmental programs of plants. Its signaling depends primarily on its perception by four partially redundant receptors of the TIR1/AFB2 clade (TAARs), which subsequently mediate the specific degradation of AUX/IAA transcriptional repressors to modulate the expression of primary auxin-responsive genes. Auxin homeostasis depends on complex regulations at the level of synthesis, conjugation, and transport. However, the mechanisms and principles involved in the homeostasis of its signaling are just starting to emerge. We report that xrn4 mutants exhibit pleiotropic developmental defects and strong auxin hypersensitivity phenotypes. We provide compelling evidences that these phenotypes are directly caused by improper regulation of TAAR transcript degradation. We show that the cytoplasmic 5′-3′ exoribonuclease XRN4 is required for auxin response. Thus, our work identifies new targets of XRN4 and a new level of regulation for TAAR transcripts important for auxin response and for plant development. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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12 pages, 534 KiB

Open AccessArticle

A Systematic Study on DNA Barcoding of Medicinally Important Genus Epimedium L. (Berberidaceae)

by Mengyue Guo¹

, Yanqin Xu², Li Ren¹, Shunzhi He³ and Xiaohui Pang^1,*

¹ Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

³ Department of Pharmacy, Guiyang College of Traditional Chinese Medicine, Guiyang 550002, China

Genes 2018, 9(12), 637; https://doi.org/10.3390/genes9120637 - 17 Dec 2018

Cited by 19 | Viewed by 4988

Abstract

Genus Epimedium consists of approximately 50 species in China, and more than half of them possess medicinal properties. The high similarity of species’ morphological characteristics complicates the identification accuracy, leading to potential risks in herbal efficacy and medical safety. In this study, we [...] Read more.

Genus Epimedium consists of approximately 50 species in China, and more than half of them possess medicinal properties. The high similarity of species’ morphological characteristics complicates the identification accuracy, leading to potential risks in herbal efficacy and medical safety. In this study, we tested the applicability of four single loci, namely, rbcL, psbA-trnH, internal transcribed spacer (ITS), and ITS2, and their combinations as DNA barcodes to identify 37 Epimedium species on the basis of the analyses, including the success rates of PCR amplifications and sequencing, specific genetic divergence, distance-based method, and character-based method. Among them, character-based method showed the best applicability for identifying Epimedium species. As for the DNA barcodes, psbA-trnH showed the best performance among the four single loci with nine species being correctly differentiated. Moreover, psbA-trnH + ITS and psbA-trnH + ITS + rbcL exhibited the highest identification ability among all the multilocus combinations, and 17 species, of which 12 are medicinally used, could be efficiently discriminated. The DNA barcode data set developed in our study contributes valuable information to Chinese resources of Epimedium. It provides a new means for discrimination of the species within this medicinally important genus, thus guaranteeing correct and safe usage of Herba Epimedii. Full article

(This article belongs to the Special Issue DNA Barcoding and Metabarcoding of Complex Matrices)

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13 pages, 1793 KiB

Open AccessArticle

Genome Based Meta-QTL Analysis of Grain Weight in Tetraploid Wheat Identifies Rare Alleles of GRF4 Associated with Larger Grains

by Raz Avni¹

, Leah Oren^1,2, Gai Shabtay¹, Siwar Assili^2,3, Curtis Pozniak⁴, Iago Hale⁵, Roi Ben-David³, Zvi Peleg²

and Assaf Distelfeld^1,*

¹ School of Plant Sciences and Food Security, Tel Aviv University, Tel Aviv 6997801, Israel

² The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel

³ The Institute of Plant Sciences, Agriculture Research Organization (ARO)—Volcani, Rishon LeZion 7505101, Israel

⁴ University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada

⁵ Department of Agriculture, Nutrition, and Food Systems, University of New Hampshire, Durham, NH 03824, USA

Genes 2018, 9(12), 636; https://doi.org/10.3390/genes9120636 - 17 Dec 2018

Cited by 40 | Viewed by 6318

Abstract

The domestication and subsequent genetic improvement of wheat led to the development of large-seeded cultivated wheat species relative to their smaller-seeded wild progenitors. While increased grain weight (GW) continues to be an important goal of many wheat breeding programs, few genes underlying this [...] Read more.

The domestication and subsequent genetic improvement of wheat led to the development of large-seeded cultivated wheat species relative to their smaller-seeded wild progenitors. While increased grain weight (GW) continues to be an important goal of many wheat breeding programs, few genes underlying this trait have been identified despite an abundance of studies reporting quantitative trait loci (QTL) for GW. Here we perform a QTL analysis for GW using a population of recombinant inbred lines (RILs) derived from the cross between wild emmer wheat accession ‘Zavitan’ and durum wheat variety ‘Svevo’. Identified QTLs in this population were anchored to the recent Zavitan reference genome, along with previously published QTLs for GW in tetraploid wheat. This genome-based, meta-QTL analysis enabled the identification of a locus on chromosome 6A whose introgression from wild wheat positively affects GW. The locus was validated using an introgression line carrying the 6A GW QTL region from Zavitan in a Svevo background, resulting in >8% increase in GW compared to Svevo. Using the reference sequence for the 6A QTL region, we identified a wheat ortholog to OsGRF4, a rice gene previously associated with GW. The coding sequence of this gene (TtGRF4-A) contains four single nucleotide polymorphisms (SNPs) between Zavitan and Svevo, one of which reveals the Zavitan allele to be rare in a core collection of wild emmer and completely absent from the domesticated emmer genepool. Similarly, another wild emmer accession (G18-16) was found to carry a rare allele of TtGRF4-A that also positively affects GW and is characterized by a unique SNP absent from the entire core collection. These results exemplify the rich genetic diversity of wild wheat, posit TtGRF4-A as a candidate gene underlying the 6A GW QTL, and suggest that the natural Zavitan and G18-16 alleles of TtGRF4-A have potential to increase wheat yields in breeding programs. Full article

(This article belongs to the Special Issue Genomics of Plant Domestication and Crop Evolution)

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15 pages, 3781 KiB

Open AccessArticle

The Yellow Stripe-Like (YSL) Gene Functions in Internal Copper Transport in Peanut

by Jing Dai^1,2,†, Nanqi Wang^1,†, Hongchun Xiong³, Wei Qiu¹

, Hiromi Nakanishi², Takanori Kobayashi⁴, Naoko K. Nishizawa^2,4 and Yuanmei Zuo^1,*

¹ Key Lab of Plant-Soil Interaction, MOE, Center for Resources, Environment and Food Security, College Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China

² Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

³ Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China

⁴ Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa 921-8836, Japan

^† These authors contribute equally to this work.

Genes 2018, 9(12), 635; https://doi.org/10.3390/genes9120635 - 14 Dec 2018

Cited by 33 | Viewed by 5968

Abstract

Copper (Cu) is involved in fundamental biological processes for plant growth and development. However, Cu excess is harmful to plants. Thus, Cu in plant tissues must be tightly regulated. In this study, we found that the peanut Yellow Stripe-Like family gene AhYSL3.1 is [...] Read more.

Copper (Cu) is involved in fundamental biological processes for plant growth and development. However, Cu excess is harmful to plants. Thus, Cu in plant tissues must be tightly regulated. In this study, we found that the peanut Yellow Stripe-Like family gene AhYSL3.1 is involved in Cu transport. Among five AhYSL genes, AhYSL3.1 and AhYSL3.2 were upregulated by Cu deficiency in peanut roots and expressed mainly in young leaves. A yeast complementation assay suggested that the plasma membrane-localized AhYSL3.1 was a Cu-nicotianamine complex transporter. High expression of AhYSL3.1 in tobacco and rice plants with excess Cu resulted in a low concentration of Cu in young leaves. These transgenic plants were resistant to excess Cu. The above results suggest that AhYSL3.1 is responsible for the internal transport of Cu in peanut. Full article

(This article belongs to the Special Issue Improving Plant Nutrient Use efficiency)

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21 pages, 2022 KiB

Open AccessReview

Regulation of Structure-Specific Endonucleases in Replication Stress

by Seong Min Kim and Susan L. Forsburg^*

Program in Molecular & Computational Biology, University of Southern California, Los Angeles, CA 90089, USA

Genes 2018, 9(12), 634; https://doi.org/10.3390/genes9120634 - 14 Dec 2018

Cited by 11 | Viewed by 5501

Abstract

Replication stress results in various forms of aberrant replication intermediates that need to be resolved for faithful chromosome segregation. Structure-specific endonucleases (SSEs) recognize DNA secondary structures rather than primary sequences and play key roles during DNA repair and replication stress. Holliday junction resolvase [...] Read more.

Replication stress results in various forms of aberrant replication intermediates that need to be resolved for faithful chromosome segregation. Structure-specific endonucleases (SSEs) recognize DNA secondary structures rather than primary sequences and play key roles during DNA repair and replication stress. Holliday junction resolvase MUS81 (methyl methane sulfonate (MMS), and UV-sensitive protein 81) and XPF (xeroderma pigmentosum group F-complementing protein) are a subset of SSEs that resolve aberrant replication structures. To ensure genome stability and prevent unnecessary DNA breakage, these SSEs are tightly regulated by the cell cycle and replication checkpoints. We discuss the regulatory network that control activities of MUS81 and XPF and briefly mention other SSEs involved in the resolution of replication intermediates. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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18 pages, 1727 KiB

Open AccessReview

Enhancing the Anticancer Efficacy of Immunotherapy through Combination with Histone Modification Inhibitors

by Wanyu Sun, Shuting Lv, Hong Li, Wei Cui^* and Lihui Wang^*

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China

Genes 2018, 9(12), 633; https://doi.org/10.3390/genes9120633 - 14 Dec 2018

Cited by 31 | Viewed by 6450

Abstract

In the nucleus of each cell, the DNA is wrapped around histone octamers, forming the so-called “nucleosomal core particles”. The histones undergo various modifications that influence chromatin structure and function, including methylation, acetylation, ubiquitination, phosphorylation, and SUMOylation. These modifications, known as epigenetic modifications [...] Read more.

In the nucleus of each cell, the DNA is wrapped around histone octamers, forming the so-called “nucleosomal core particles”. The histones undergo various modifications that influence chromatin structure and function, including methylation, acetylation, ubiquitination, phosphorylation, and SUMOylation. These modifications, known as epigenetic modifications (defined as heritable molecular determinants of phenotype that are independent of the DNA sequence), result in alterations of gene expression and changes in cell behavior. Recent work has shown that epigenetic drugs targeting histone deacetylation or methylation modulate the immune response and overcome acquired resistance to immunotherapy. A number of combination therapies involving immunotherapy and epigenetic drugs, which target histone deacetylation or methylation, are currently under various clinical/pre-clinical investigations and have shown promising anticancer efficacy. These combination therapies may provide a new strategy for achieving sustained anticancer efficacy and overcoming resistance. Full article

(This article belongs to the Special Issue Histone Modification Enzymes and Long Noncoding RNAs in Cancer)

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31 pages, 1316 KiB

Open AccessReview

Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and Methods for Genome-Wide Profiling

by Britta A. M. Bouwman^*

and Nicola Crosetto^*

Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17165 Stockholm, Sweden

Genes 2018, 9(12), 632; https://doi.org/10.3390/genes9120632 - 14 Dec 2018

Cited by 40 | Viewed by 10376

Abstract

DNA double-strand breaks (DSBs) jeopardize genome integrity and can—when repaired unfaithfully—give rise to structural rearrangements associated with cancer. Exogenous agents such as ionizing radiation or chemotherapy can invoke DSBs, but a vast amount of breakage arises during vital endogenous DNA transactions, such as [...] Read more.

DNA double-strand breaks (DSBs) jeopardize genome integrity and can—when repaired unfaithfully—give rise to structural rearrangements associated with cancer. Exogenous agents such as ionizing radiation or chemotherapy can invoke DSBs, but a vast amount of breakage arises during vital endogenous DNA transactions, such as replication and transcription. Additionally, chromatin looping involved in 3D genome organization and gene regulation is increasingly recognized as a possible contributor to DSB events. In this review, we first discuss insights into the mechanisms of endogenous DSB formation, showcasing the trade-off between essential DNA transactions and the intrinsic challenges that these processes impose on genomic integrity. In the second part, we highlight emerging methods for genome-wide profiling of DSBs, and discuss future directions of research that will help advance our understanding of genome-wide DSB formation and repair. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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22 pages, 360 KiB

Open AccessArticle

Association between Polymorphisms in Inflammatory Response-Related Genes and the Susceptibility, Progression and Prognosis of the Diffuse Histological Subtype of Gastric Cancer

by Tatiane K. Furuya^1,*, Carlos E. Jacob^2,†, Michele T. P. Tomitão^1,3, Lizeth C. C. Camacho¹, Marcus F. K. P. Ramos³

, José Eluf-Neto⁴

, Venâncio A. F. Alves^5,6, Bruno Zilberstein², Ivan Cecconello², Ulysses Ribeiro, Jr.³

and Roger Chammas¹

¹ Centro de Investigacao Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo 01246-000, Brazil

² Departamento de Gastroenterologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo 01246-000, Brazil

³ Departamento de Gastroenterologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP); Instituto do Cancer do Estado de Sao Paulo (ICESP), Sao Paulo 01246-000, Brazil

⁴ Laboratorio de Epidemiologia e Imunobiologia (LIM38), Departamento de Medicina Preventiva, Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo 01246-000, Brazil

⁵ Departamento de Patologia (LIM14), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo 01246-000, Brazil

⁶ CICAP, Anatomia Patologica, Hospital Alemao Oswaldo Cruz, Sao Paulo 01327-001, Brazil

^† This paper is dedicated to the memory of Dr Carlos E Jacob, who recently passed away.

Genes 2018, 9(12), 631; https://doi.org/10.3390/genes9120631 - 13 Dec 2018

Cited by 20 | Viewed by 4451

Abstract

The chronic inflammatory microenvironment and immune cell dysfunction have been described as critical components for gastric tumor initiation and progression. The diffuse subtype is related to poor clinical outcomes, pronounced inflammation, and the worst prognosis. We investigated the association of polymorphisms in inflammatory [...] Read more.

The chronic inflammatory microenvironment and immune cell dysfunction have been described as critical components for gastric tumor initiation and progression. The diffuse subtype is related to poor clinical outcomes, pronounced inflammation, and the worst prognosis. We investigated the association of polymorphisms in inflammatory response-related genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB, and TP53) with gastric cancer susceptibility, progression and prognosis in a Brazilian sample, focusing on the diffuse subtype. We also performed the analysis regarding the total sample of cases (not stratified for tumor subtypes), allowing the comparison between the findings. We further investigated the polymorphisms in linkage disequilibrium and performed haplotype association analyses. In the case-control study, rs1042522 (TP53) was associated with a stronger risk for developing gastric cancer in the sample stratified for diffuse subtype patients when compared to the risk observed for the total cases; CTC haplotype (rs699947/rs833061/rs2010963 VEGFA) was associated with risk while rs699947 was associated with protection for gastric malignancy in the total sample. Regarding the associations with the clinicopathological features of gastric cancer, for the diffuse subtype we found that rs699947 and rs833061 (VEGFA) were associated with outcomes related to a worse progression while rs5275 (COX-2), rs909253 (TNFB), and rs2227956 (HSPA1L) were associated to a better progression of the disease. In the total sample, rs699947 and rs833061 (VEGFA), rs4644 (LGALS3), and rs1042522 (TP53) were able to predict a worse progression while rs5275 (COX-2), rs2227956 (HSPA1L), and rs3025039 (VEGFA) a better progression. Besides, rs909253 (TNFB) predicted protection for the overall and disease-free survivals for gastric cancer. In conclusion, these results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric cancer. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Complex Diseases in Latin America)

19 pages, 3419 KiB

Open AccessArticle

Enhancer Trapping and Annotation in Zebrafish Mediated with Sleeping Beauty, piggyBac and Tol2 Transposons

by Dan Shen^1,†, Songlei Xue^1,†, Shuheng Chan¹, Yatong Sang¹, Saisai Wang¹, Yali Wang¹, Cai Chen¹, Bo Gao¹

, Ferenc Mueller² and Chengyi Song^1,*

¹ Institute of Mobilome and Genome, College of Animal Science & Technology, Yangzhou University, Yangzhou 225009, China

² Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

^† These authors contributed equally to this work.

Genes 2018, 9(12), 630; https://doi.org/10.3390/genes9120630 - 13 Dec 2018

Cited by 8 | Viewed by 6396

Abstract

Although transposon-mediated enhancer trapping (ET) is successfully applied in diverse models, the efficiency of various transposon systems varies significantly, and little information is available regarding efficiency of enhancer trapping by various transposons in zebrafish. Most potential enhancers (Ens) still lack evidence of actual [...] Read more.

Although transposon-mediated enhancer trapping (ET) is successfully applied in diverse models, the efficiency of various transposon systems varies significantly, and little information is available regarding efficiency of enhancer trapping by various transposons in zebrafish. Most potential enhancers (Ens) still lack evidence of actual En activity. Here, we compared the differences in ET efficiency between sleeping beauty (SB), piggyBac (PB) and Tol2 transposons. Tol2 represented the highest germline transfer efficiencies at 55.56% (N_F0 = 165), followed by SB (38.36%, N_F0 = 151) and PB (32.65%, N_F0 = 149). ET lines generated by the Tol2 transposon tended to produce offspring with a single expression pattern per line, while PB and SB tended to generate embryos with multiple expression patterns. In our tests, 10 putative Ens (En1–10) were identified by splinkerette PCR and comparative genomic analysis. Combining the GFP expression profiles and mRNA expression patterns revealed that En1 and En2 may be involved in regulation of the expression of dlx1a and dlx2a, while En6 may be involved in regulation of the expression of line TK4 transgene and rps26, and En7 may be involved in the regulation of the expression of wnt1 and wnt10b. Most identified Ens were found to be transcribed in zebrafish embryos, and their regulatory function may involve eRNAs. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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23 pages, 1296 KiB

Open AccessReview

RAD-ical New Insights into RAD51 Regulation

by Meghan R. Sullivan and Kara A. Bernstein^*

Department of Microbiology and Molecular Genetics, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA

Genes 2018, 9(12), 629; https://doi.org/10.3390/genes9120629 - 13 Dec 2018

Cited by 99 | Viewed by 13137

Abstract

The accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions; however, they can be repaired using homologous recombination. Homologous recombination is a high-fidelity DNA repair pathway that uses a homologous [...] Read more.

The accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions; however, they can be repaired using homologous recombination. Homologous recombination is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, which is a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, which are collectively termed the RAD51 mediators. The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Mutations in the human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1) are found in a subset of breast and ovarian cancers. Despite their discovery three decades ago, few advances have been made in understanding the function of the human RAD51 paralogs. Here, we discuss the current perspective on the in vivo and in vitro function of the RAD51 paralogs, and their relationship with cancer in vertebrate models. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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11 pages, 1797 KiB

Open AccessArticle

PIF-Mediated Sucrose Regulation of the Circadian Oscillator is Light Quality and Temperature Dependent

by Ekaterina Shor¹

, Raya Potavskaya¹, Ayelet Kurtz¹, Inyup Paik², Enamul Huq²

and Rachel Green^1,*

¹ Department of Plant and Environmental Sciences, Institute for Life Sciences, Edmond J. Safra Campus, Givat Ram, Hebrew University, Jerusalem, 91904 Israel

² Department of Molecular Biosciences and The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA

Genes 2018, 9(12), 628; https://doi.org/10.3390/genes9120628 - 13 Dec 2018

Cited by 15 | Viewed by 4668

Abstract

Studies are increasingly showing that metabolic and circadian (~24 h) pathways are strongly interconnected, with the circadian system regulating the metabolic state of the cell, and metabolic products feeding back to entrain the oscillator. In plants, probably the most significant impact of the [...] Read more.

Studies are increasingly showing that metabolic and circadian (~24 h) pathways are strongly interconnected, with the circadian system regulating the metabolic state of the cell, and metabolic products feeding back to entrain the oscillator. In plants, probably the most significant impact of the circadian system on metabolism is in its reciprocal regulation of photosynthesis; however, the pathways by which this occurs are still poorly understood. We have previously shown that members of the basic helix-loop-helix (bHLH) transcription factor PHYTOCHROME INTERACTING FACTOR (PIF) family are involved in the photosynthate entrainment of the circadian oscillator. In this paper, using Arabidopsis mutants and overexpression lines, we examine how temperature and light quality affect PIF-mediated sucrose signaling to the oscillator and examine the contributions of individual PIF members. Our results also show that the quality of light is important for PIF signaling, with red and blue lights having the opposite effects, and that temperature affects PIF-mediated sucrose signaling. We propose the light sensitivity of PIF-mediated sucrose entrainment of the oscillator may be important in enabling plants to distinguish between sucrose produced de novo from photosynthesis during the day and the sucrose products of starch degradation at the end of the night. Full article

(This article belongs to the Special Issue Genetic Regulation of Circadian Rhythm in Plants)

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13 pages, 2284 KiB

Open AccessArticle

A-to-I RNA Editing Affects lncRNAs Expression after Heat Shock

by Roni Haas, Nabeel S. Ganem

, Ayya Keshet, Angela Orlov, Alla Fishman and Ayelet T. Lamm^*

Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel

Genes 2018, 9(12), 627; https://doi.org/10.3390/genes9120627 - 13 Dec 2018

Cited by 6 | Viewed by 4777

Abstract

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on double-stranded RNA (dsRNAs). Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in [...] Read more.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on double-stranded RNA (dsRNAs). Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant Caenorhabditis elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that long non-coding RNAs (lncRNAs) and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function. Full article

(This article belongs to the Special Issue RNA Modifications)

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30 pages, 2724 KiB

Open AccessArticle

Neural Network Evolving Algorithm Based on the Triplet Codon Encoding Method

by Xu Yang^*

, Songgaojun Deng

, Mengyao Ji, Jinfeng Zhao and Wenhao Zheng

School of Computer Science and Technology, Beijing Institute of Technology, Beijing 100081, China

Genes 2018, 9(12), 626; https://doi.org/10.3390/genes9120626 - 13 Dec 2018

Cited by 3 | Viewed by 4633

Abstract

Artificial intelligence research received more and more attention nowadays. Neural Evolution (NE) is one very important branch of AI, which waves the power of evolutionary algorithms to generate Artificial Neural Networks (ANNs). How to use the evolutionary advantages of network topology and weights [...] Read more.

Artificial intelligence research received more and more attention nowadays. Neural Evolution (NE) is one very important branch of AI, which waves the power of evolutionary algorithms to generate Artificial Neural Networks (ANNs). How to use the evolutionary advantages of network topology and weights to solve the application of Artificial Neural Networks is the main problem in the field of NE. In this paper, a novel DNA encoding method based on the triple codon is proposed. Additionally, a NE algorithm Triplet Codon Encoding Neural Network Evolving Algorithm (TCENNE) based on this encoding method is presented to verify the rationality and validity of the coding design. The results show that TCENNE is very effective and more robust than NE algorithms, due to the coding design. Also, it is shown that it can realize the co-evolution of network topology and weights and outperform other neural evolution systems in challenging reinforcement learning tasks. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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18 pages, 3461 KiB

Open AccessArticle

Ancient Ancestry Informative Markers for Identifying Fine-Scale Ancient Population Structure in Eurasians

by Umberto Esposito¹, Ranajit Das²

, Syakir Syed¹, Mehdi Pirooznia³

and Eran Elhaik^1,*

¹ Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, UK

² Manipal University, Manipal Centre for Natural Sciences (MCNS), Manipal, Karnataka 576104, India

³ Bioinformatics and Computational Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

Genes 2018, 9(12), 625; https://doi.org/10.3390/genes9120625 - 12 Dec 2018

Cited by 13 | Viewed by 11457

Abstract

The rapid accumulation of ancient human genomes from various areas and time periods potentially enables the expansion of studies of biodiversity, biogeography, forensics, population history, and epidemiology into past populations. However, most ancient DNA (aDNA) data were generated through microarrays designed for modern-day [...] Read more.

The rapid accumulation of ancient human genomes from various areas and time periods potentially enables the expansion of studies of biodiversity, biogeography, forensics, population history, and epidemiology into past populations. However, most ancient DNA (aDNA) data were generated through microarrays designed for modern-day populations, which are known to misrepresent the population structure. Past studies addressed these problems by using ancestry informative markers (AIMs). It is, however, unclear whether AIMs derived from contemporary human genomes can capture ancient population structures, and whether AIM-finding methods are applicable to aDNA. Further the high missingness rates in ancient—and oftentimes haploid—DNA can also distort the population structure. Here, we define ancient AIMs (aAIMs) and develop a framework to evaluate established and novel AIM-finding methods in identifying the most informative markers. We show that aAIMs identified by a novel principal component analysis (PCA)-based method outperform all of the competing methods in classifying ancient individuals into populations and identifying admixed individuals. In some cases, predictions made using the aAIMs were more accurate than those made with a complete marker set. We discuss the features of the ancient Eurasian population structure and strategies to identify aAIMs. This work informs the design of single nucleotide polymorphism (SNP) microarrays and the interpretation of aDNA results, which enables a population-wide testing of primordialist theories. Full article

(This article belongs to the Special Issue Tools for Population and Evolutionary Genetics)

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22 pages, 4195 KiB

Open AccessArticle

Transcriptome Analysis Reveals Candidate Genes for Cold Tolerance in Drosophila ananassae

by Annabella Königer and Sonja Grath^*

Division of Evolutionary Biology, Faculty of Biology, LMU Munich, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany

Genes 2018, 9(12), 624; https://doi.org/10.3390/genes9120624 - 12 Dec 2018

Cited by 18 | Viewed by 5609

Abstract

Coping with daily and seasonal temperature fluctuations is a key adaptive process for species to colonize temperate regions all over the globe. Over the past 18,000 years, the tropical species Drosophila ananassae expanded its home range from tropical regions in Southeast Asia to [...] Read more.

Coping with daily and seasonal temperature fluctuations is a key adaptive process for species to colonize temperate regions all over the globe. Over the past 18,000 years, the tropical species Drosophila ananassae expanded its home range from tropical regions in Southeast Asia to more temperate regions. Phenotypic assays of chill coma recovery time (CCRT) together with previously published population genetic data suggest that only a small number of genes underlie improved cold hardiness in the cold-adapted populations. We used high-throughput RNA sequencing to analyze differential gene expression before and after exposure to a cold shock in coldtolerant lines (those with fast chill coma recovery, CCR) and cold-sensitive lines (slow CCR) from a population originating from Bangkok, Thailand (the ancestral species range). We identified two candidate genes with a significant interaction between cold tolerance and cold shock treatment: GF14647 and GF15058. Further, our data suggest that selection for increased cold tolerance did not operate through the increased activity of heat shock proteins, but more likely through the stabilization of the actin cytoskeleton and a delayed onset of apoptosis. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Gene Expression)

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16 pages, 2625 KiB

Open AccessReview

The Unresolved Problem of DNA Bridging

by María Fernández-Casañas and Kok-Lung Chan^*

Chromosome Dynamics and Stability Group, Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK

Genes 2018, 9(12), 623; https://doi.org/10.3390/genes9120623 - 12 Dec 2018

Cited by 30 | Viewed by 8449

Abstract

Accurate duplication and transmission of identical genetic information into offspring cells lies at the heart of a cell division cycle. During the last stage of cellular division, namely mitosis, the fully replicated DNA molecules are condensed into X-shaped chromosomes, followed by a chromosome [...] Read more.

Accurate duplication and transmission of identical genetic information into offspring cells lies at the heart of a cell division cycle. During the last stage of cellular division, namely mitosis, the fully replicated DNA molecules are condensed into X-shaped chromosomes, followed by a chromosome separation process called sister chromatid disjunction. This process allows for the equal partition of genetic material into two newly born daughter cells. However, emerging evidence has shown that faithful chromosome segregation is challenged by the presence of persistent DNA intertwining structures generated during DNA replication and repair, which manifest as so-called ultra-fine DNA bridges (UFBs) during anaphase. Undoubtedly, failure to disentangle DNA linkages poses a severe threat to mitosis and genome integrity. This review will summarize the possible causes of DNA bridges, particularly sister DNA inter-linkage structures, in an attempt to explain how they may be processed and how they influence faithful chromosome segregation and the maintenance of genome stability. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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17 pages, 871 KiB

Open AccessReview

Chromatin as a Platform for Modulating the Replication Stress Response

by Louis-Alexandre Fournier^1,†, Arun Kumar^1,† and Peter C. Stirling^1,2,*

¹ Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada

² Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 1L3, Canada

^† These authors have contributed equally to this work.

Genes 2018, 9(12), 622; https://doi.org/10.3390/genes9120622 - 11 Dec 2018

Cited by 15 | Viewed by 7397

Abstract

Eukaryotic DNA replication occurs in the context of chromatin. Recent years have seen major advances in our understanding of histone supply, histone recycling and nascent histone incorporation during replication. Furthermore, much is now known about the roles of histone remodellers and post-translational modifications [...] Read more.

Eukaryotic DNA replication occurs in the context of chromatin. Recent years have seen major advances in our understanding of histone supply, histone recycling and nascent histone incorporation during replication. Furthermore, much is now known about the roles of histone remodellers and post-translational modifications in replication. It has also become clear that nucleosome dynamics during replication play critical roles in genome maintenance and that chromatin modifiers are important for preventing DNA replication stress. An understanding of how cells deploy specific nucleosome modifiers, chaperones and remodellers directly at sites of replication fork stalling has been building more slowly. Here we will specifically discuss recent advances in understanding how chromatin composition contribute to replication fork stability and restart. Full article

(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)

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14 pages, 4226 KiB

Open AccessReview

DNA-Based Super-Resolution Microscopy: DNA-PAINT

by Daniel J. Nieves^1,2

, Katharina Gaus^1,2 and Matthew A. B. Baker^3,4,*

¹ EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia

² ARC Center of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW 2052, Australia

³ School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia

⁴ CSIRO Synthetic Biology Future Science Platform, GPO Box 2583, Brisbane, QLD 4001, Australia

Genes 2018, 9(12), 621; https://doi.org/10.3390/genes9120621 - 11 Dec 2018

Cited by 59 | Viewed by 19339

Abstract

Super-resolution microscopies, such as single molecule localization microscopy (SMLM), allow the visualization of biomolecules at the nanoscale. The requirement to observe molecules multiple times during an acquisition has pushed the field to explore methods that allow the binding of a fluorophore to a [...] Read more.

Super-resolution microscopies, such as single molecule localization microscopy (SMLM), allow the visualization of biomolecules at the nanoscale. The requirement to observe molecules multiple times during an acquisition has pushed the field to explore methods that allow the binding of a fluorophore to a target. This binding is then used to build an image via points accumulation for imaging nanoscale topography (PAINT), which relies on the stochastic binding of a fluorescent ligand instead of the stochastic photo-activation of a permanently bound fluorophore. Recently, systems that use DNA to achieve repeated, transient binding for PAINT imaging have become the cutting edge in SMLM. Here, we review the history of PAINT imaging, with a particular focus on the development of DNA-PAINT. We outline the different variations of DNA-PAINT and their applications for imaging of both DNA origamis and cellular proteins via SMLM. Finally, we reflect on the current challenges for DNA-PAINT imaging going forward. Full article

(This article belongs to the Special Issue DNA Origami and Aptamer Assemblies)

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20 pages, 10847 KiB

Open AccessReview

Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation

by Wendan Ren^1,†, Linfeng Gao^2,†

and Jikui Song^1,2,*

¹ Department of Biochemistry, University of California, Riverside, CA 92521, USA

² Environmental Toxicology Program, University of California, Riverside, CA 92521, USA

^† These authors contributed equally to this work.

Genes 2018, 9(12), 620; https://doi.org/10.3390/genes9120620 - 11 Dec 2018

Cited by 105 | Viewed by 17822

Abstract

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. The establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which [...] Read more.

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. The establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-domain proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1 and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains. Full article

(This article belongs to the Special Issue Role of DNA Methyltransferases in the Epigenome)

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8 pages, 2531 KiB

Open AccessArticle

RNA Modification Level Estimation with pulseR

by Etienne Boileau^1,2,*

and Christoph Dieterich^1,2,*

¹ Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology and Department of Internal Medicine III, University Hospital Heidelberg, 69120 Heidelberg, Germany

² German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

Genes 2018, 9(12), 619; https://doi.org/10.3390/genes9120619 - 10 Dec 2018

Cited by 2 | Viewed by 4484

Abstract

RNA modifications regulate the complex life of transcripts. An experimental approach called LAIC-seq was developed to characterize modification levels on a transcriptome-wide scale. In this method, the modified and unmodified molecules are separated using antibodies specific for a given RNA modification (e.g., m [...] Read more.

RNA modifications regulate the complex life of transcripts. An experimental approach called LAIC-seq was developed to characterize modification levels on a transcriptome-wide scale. In this method, the modified and unmodified molecules are separated using antibodies specific for a given RNA modification (e.g., m⁶A). In essence, the procedure of biochemical separation yields three fractions: Input, eluate, and supernatent, which are subjected to RNA-seq. In this work, we present a bioinformatics workflow, which starts from RNA-seq data to infer gene-specific modification levels by a statistical model on a transcriptome-wide scale. Our workflow centers around the pulseR package, which was originally developed for the analysis of metabolic labeling experiments. We demonstrate how to analyze data without external normalization (i.e., in the absence of spike-ins), given high efficiency of separation, and how, alternatively, scaling factors can be derived from unmodified spike-ins. Importantly, our workflow provides an estimate of uncertainty of modification levels in terms of confidence intervals for model parameters, such as gene expression and RNA modification levels. We also compare alternative model parametrizations, log-odds, or the proportion of the modified molecules and discuss the pros and cons of each representation. In summary, our workflow is a versatile approach to RNA modification level estimation, which is open to any read-count-based experimental approach. Full article

(This article belongs to the Special Issue RNA Modifications)

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12 pages, 2389 KiB

Open AccessArticle

Rediscovery of Red Wolf Ghost Alleles in a Canid Population Along the American Gulf Coast

by Elizabeth Heppenheimer^1,†

, Kristin E. Brzeski^1,2,*,†, Ron Wooten³, William Waddell⁴, Linda Y. Rutledge^1,5, Michael J. Chamberlain⁶, Daniel R. Stahler⁷, Joseph W. Hinton⁶

and Bridgett M. VonHoldt^1,*

¹ Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA

² School of Forest Resources & Environmental Science, Michigan Technological University, Houghton, MI 49931, USA

³ Wildlife Biologist, Galveston, TX 77550, USA

⁴ Zoological and Environmental Education Department, Point Defiance Zoo & Aquarium, Tacoma, WA 98407, USA

⁵ Biology Department, Trent University, Peterborough, ON K9L 1Z8, Canada

⁶ Warnell School of Forestry and Natural Resources, University of Georgia, Athens, GA 30602, USA

⁷ Yellowstone Center for Resources, National Park Service, Yellowstone National Park, WY 82190, USA

^† These authors contributed equally to this work.

Genes 2018, 9(12), 618; https://doi.org/10.3390/genes9120618 - 10 Dec 2018

Cited by 24 | Viewed by 23925

Abstract

Rediscovering species once thought to be extinct or on the edge of extinction is rare. Red wolves have been extinct along the American Gulf Coast since 1980, with their last populations found in coastal Louisiana and Texas. We report the rediscovery of red [...] Read more.

Rediscovering species once thought to be extinct or on the edge of extinction is rare. Red wolves have been extinct along the American Gulf Coast since 1980, with their last populations found in coastal Louisiana and Texas. We report the rediscovery of red wolf ghost alleles in a canid population on Galveston Island, Texas. We analyzed over 7000 single nucleotide polymorphisms (SNPs) in 60 canid representatives from all legally recognized North American Canis species and two phenotypically ambiguous canids from Galveston Island. We found notably high Bayesian cluster assignments of the Galveston canids to captive red wolves with extensive sharing of red wolf private alleles. Today, the only known extant wild red wolves persist in a reintroduced population in North Carolina, which is dwindling amongst political and taxonomic controversy. Our rediscovery of red wolf ancestry after almost 40 years introduces both positive opportunities for additional conservation action and difficult policy challenges. Full article

(This article belongs to the Special Issue Conservation Genetics and Genomics)

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18 pages, 1557 KiB

Open AccessReview

Mechanisms of DNA Methyltransferase Recruitment in Mammals

by Marthe Laisné¹, Nikhil Gupta¹

, Olivier Kirsh¹

, Sriharsa Pradhan² and Pierre-Antoine Defossez^1,*

¹ Epigenetics and Cell Fate, UMR7216 CNRS, University Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France

² New England Biolabs, 240 County Rd, Ipswich, MA 01938, USA

Genes 2018, 9(12), 617; https://doi.org/10.3390/genes9120617 - 10 Dec 2018

Cited by 36 | Viewed by 9143

Abstract

DNA methylation is an essential epigenetic mark in mammals. The proper distribution of this mark depends on accurate deposition and maintenance mechanisms, and underpins its functional role. This, in turn, depends on the precise recruitment and activation of de novo and maintenance DNA [...] Read more.

DNA methylation is an essential epigenetic mark in mammals. The proper distribution of this mark depends on accurate deposition and maintenance mechanisms, and underpins its functional role. This, in turn, depends on the precise recruitment and activation of de novo and maintenance DNA methyltransferases (DNMTs). In this review, we discuss mechanisms of recruitment of DNMTs by transcription factors and chromatin modifiers—and by RNA—and place these mechanisms in the context of biologically meaningful epigenetic events. We present hypotheses and speculations for future research, and underline the fundamental and practical benefits of better understanding the mechanisms that govern the recruitment of DNMTs. Full article

(This article belongs to the Special Issue Role of DNA Methyltransferases in the Epigenome)

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Beyond Transcription: Fine-Tuning of Circadian Timekeeping by Post-Transcriptional Regulation

by Julieta Lisa Mateos^1,*

, Maria José De Leone¹

, Jeanette Torchio¹, Marlene Reichel² and Dorothee Staiger^2,*

¹ Fundación Instituto Leloir, Av. Patricias Argentinas, Buenos Aires C1405BWE, Argentina

² RNA Biology and Molecular Physiology, Faculty for Biology, Bielefeld University, Universitaetsstrasse 25, D-33615 Bielefeld, Germany

Genes 2018, 9(12), 616; https://doi.org/10.3390/genes9120616 - 10 Dec 2018

Cited by 30 | Viewed by 6272

Abstract

The circadian clock is an important endogenous timekeeper, helping plants to prepare for the periodic changes of light and darkness in their environment. The clockwork of this molecular timer is made up of clock proteins that regulate transcription of their own genes with [...] Read more.

The circadian clock is an important endogenous timekeeper, helping plants to prepare for the periodic changes of light and darkness in their environment. The clockwork of this molecular timer is made up of clock proteins that regulate transcription of their own genes with a 24 h rhythm. Furthermore, the rhythmically expressed clock proteins regulate time-of-day dependent transcription of downstream genes, causing messenger RNA (mRNA) oscillations of a large part of the transcriptome. On top of the transcriptional regulation by the clock, circadian rhythms in mRNAs rely in large parts on post-transcriptional regulation, including alternative pre-mRNA splicing, mRNA degradation, and translational control. Here, we present recent insights into the contribution of post-transcriptional regulation to core clock function and to regulation of circadian gene expression in Arabidopsis thaliana. Full article

(This article belongs to the Special Issue Genetic Regulation of Circadian Rhythm in Plants)

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Genes, Volume 9, Issue 12 (December 2018) – 79 articles

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