Demarcation of Coding and Non-Coding Regions of DNA Using Linear Transforms
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Resistance to HIV (Exercise)
1 Evolution in fast motion – Resistance to HIV (Exercise) Resistance to HIV In the early 1990s, a number of studies revealed that some people – although they had repeatedly contact with HIV – did not become carriers of HIV or, in the case of a confirmed HIV-infection, showed a delayed onset of the disease (AIDS) (a delay of several years was reported). First attempts to explain these phenomena were observed a few years later, when scientists identified important co-receptor molecules on the surface of the host cells, which are essential for HIV to infect the host cell. Scientists assumed that resistant persons may carry an aberrant version of the co-receptor molecule, which makes it impossible for the virus to enter the host cell. Such a co-receptor is the chemokine co-receptor CCR5, which is normally involved in the host’s immune answer (Dean & O’Brien, 1998). In order to test their hypothesis, the scientists sequenced the genes which code for the co- receptor CCR5. They investigated more than 700 samples from HIV-infected patients and compared them with the CCR5-sequences from more than 700 healthy persons. The results of the DNA-sequencing revealed mutations in the CCR5-gene in HIV-infected persons with a delayed onset of AIDS, as well as in some samples of healthy persons (but not in HIV- patients with typical onset of AIDS) (Samson et al., 1996). Exercises 1. In material 1, you can find two CCR5-gene-sequences selected from the data set of the scientists. Compare the sequences and a. find out where the mutation is (identify the position and label it in both! sequences). -
Insights Into Comparative Genomics, Codon Usage Bias, And
plants Article Insights into Comparative Genomics, Codon Usage Bias, and Phylogenetic Relationship of Species from Biebersteiniaceae and Nitrariaceae Based on Complete Chloroplast Genomes Xiaofeng Chi 1,2 , Faqi Zhang 1,2 , Qi Dong 1,* and Shilong Chen 1,2,* 1 Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China; [email protected] (X.C.); [email protected] (F.Z.) 2 Qinghai Provincial Key Laboratory of Crop Molecular Breeding, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China * Correspondence: [email protected] (Q.D.); [email protected] (S.C.) Received: 29 October 2020; Accepted: 17 November 2020; Published: 18 November 2020 Abstract: Biebersteiniaceae and Nitrariaceae, two small families, were classified in Sapindales recently. Taxonomic and phylogenetic relationships within Sapindales are still poorly resolved and controversial. In current study, we compared the chloroplast genomes of five species (Biebersteinia heterostemon, Peganum harmala, Nitraria roborowskii, Nitraria sibirica, and Nitraria tangutorum) from Biebersteiniaceae and Nitrariaceae. High similarity was detected in the gene order, content and orientation of the five chloroplast genomes; 13 highly variable regions were identified among the five species. An accelerated substitution rate was found in the protein-coding genes, especially clpP. The effective number of codons (ENC), parity rule 2 (PR2), and neutrality plots together revealed that the codon usage bias is affected by mutation and selection. The phylogenetic analysis strongly supported (Nitrariaceae (Biebersteiniaceae + The Rest)) relationships in Sapindales. Our findings can provide useful information for analyzing phylogeny and molecular evolution within Biebersteiniaceae and Nitrariaceae. -
Mutation Bias Shapes Gene Evolution in Arabidopsis Thaliana
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.17.156752; this version posted June 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Mutation bias shapes gene evolution in Arabidopsis thaliana 1,2† 1 1 3,4 Monroe, J. Grey , Srikant, Thanvi , Carbonell-Bejerano, Pablo , Exposito-Alonso, Moises , 5 6 7 1† Weng, Mao-Lun , Rutter, Matthew T. , Fenster, Charles B. , Weigel, Detlef 1 Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany 2 Department of Plant Sciences, University of California Davis, Davis, CA 95616, USA 3 Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA 4 Department of Biology, Stanford University, Stanford, CA 94305, USA 5 Department of Biology, Westfield State University, Westfield, MA 01086, USA 6 Department of Biology, College of Charleston, SC 29401, USA 7 Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA † corresponding authors: [email protected], [email protected] Classical evolutionary theory maintains that mutation rate variation between genes should be random with respect to fitness 1–4 and evolutionary optimization of genic 3,5 mutation rates remains controversial . However, it has now become known that cytogenetic (DNA sequence + epigenomic) features influence local mutation probabilities 6 , which is predicted by more recent theory to be a prerequisite for beneficial mutation 7 rates between different classes of genes to readily evolve . To test this possibility, we used de novo mutations in Arabidopsis thaliana to create a high resolution predictive model of mutation rates as a function of cytogenetic features across the genome. -
Lecture 1 1. to Understand the Flow of Biochemical Information from DNA to RNA to Proteins and Ultimately to Biochemical And
Lecture 1 1. To understand the flow of biochemical information from DNA to RNA to proteins and ultimately to biochemical and cellular function and dysfunction (disease) Central Dogma: DNARNAProteinPhenotype NucleotidegeneDNAchromosomegenome - In reality it is much more complex DNA sequence RNA sequence Protein sequence Protein structure Protein function RNA structure RNA function Know: - Structure of DNA/RNA and proteins - Intermolecular interactions: o Hydrogen bonds o Disulfur bonds o Ion bonds o Polar bonds - Main aspects of the central dogma o Translation (at the ribosome) o Transcription o Genetic code DNA structure: - Sugar-phosphate backbone - 4 bases o A/G = purines o T/C = pyrimidines o A-T and G-C - 5’-3’ antiparallel (always read 5’3’) o Addition occurs at the 3’ end o 5’ position to commence reading depends on promotor o Reading frame depends on promotor - Coding and template strand: o Depends on the position of the promotor RNA structure: - U replaces T - Self-complementarity = annealing of strand to itself - tRNA/mRNA/pre-RNA - Spliced (exons remain) to form mature RNA Therefore 6: - 3 from the codon from the top 5’ end, 3 from the codon from the bottom 5’ end. Protein Structure: Chemical Properties Depends on N or C-terminus, peptide bonds and side chains - Non-polar aliphatic - Polar but uncharged - Aromatic - Positively charged - Negatively charged pKa = pH at which the protein has a charge of zero. Alpha-helices: side chains point sideways Beta-helices: - Parallel and anti-parallel to produce alternate the direction the side chains point - In reality, there is a combination of parallel and anti-parallel side chains - Different bonds between NH and CO groups in each direction of side chain Sample Question 1. -
Chapter 3. the Beginnings of Genomic Biology – Molecular
Chapter 3. The Beginnings of Genomic Biology – Molecular Genetics Contents 3. The beginnings of Genomic Biology – molecular genetics 3.1. DNA is the Genetic Material 3.6.5. Translation initiation, elongation, and termnation 3.2. Watson & Crick – The structure of DNA 3.6.6. Protein Sorting in Eukaryotes 3.3. Chromosome structure 3.7. Regulation of Eukaryotic Gene Expression 3.3.1. Prokaryotic chromosome structure 3.7.1. Transcriptional Control 3.3.2. Eukaryotic chromosome structure 3.7.2. Pre-mRNA Processing Control 3.3.3. Heterochromatin & Euchromatin 3.4. DNA Replication 3.7.3. mRNA Transport from the Nucleus 3.4.1. DNA replication is semiconservative 3.7.4. Translational Control 3.4.2. DNA polymerases 3.7.5. Protein Processing Control 3.4.3. Initiation of replication 3.7.6. Degradation of mRNA Control 3.4.4. DNA replication is semidiscontinuous 3.7.7. Protein Degradation Control 3.4.5. DNA replication in Eukaryotes. 3.8. Signaling and Signal Transduction 3.4.6. Replicating ends of chromosomes 3.8.1. Types of Cellular Signals 3.5. Transcription 3.8.2. Signal Recognition – Sensing the Environment 3.5.1. Cellular RNAs are transcribed from DNA 3.8.3. Signal transduction – Responding to the Environment 3.5.2. RNA polymerases catalyze transcription 3.5.3. Transcription in Prokaryotes 3.5.4. Transcription in Prokaryotes - Polycistronic mRNAs are produced from operons 3.5.5. Beyond Operons – Modification of expression in Prokaryotes 3.5.6. Transcriptions in Eukaryotes 3.5.7. Processing primary transcripts into mature mRNA 3.6. Translation 3.6.1. -
IGA 8/E Chapter 8
8 RNA: Transcription and Processing WORKING WITH THE FIGURES 1. In Figure 8-3, why are the arrows for genes 1 and 2 pointing in opposite directions? Answer: The arrows for genes 1 and 2 indicate the direction of transcription, which is always 5 to 3. The two genes are transcribed from opposite DNA strands, which are antiparallel, so the genes must be transcribed in opposite directions to maintain the 5 to 3 direction of transcription. 2. In Figure 8-5, draw the “one gene” at much higher resolution with the following components: DNA, RNA polymerase(s), RNA(s). Answer: At the higher resolution, the feathery structures become RNA transcripts, with the longer transcripts occurring nearer the termination of the gene. The RNA in this drawing has been straightened out to illustrate the progressively longer transcripts. 3. In Figure 8-6, describe where the gene promoter is located. Chapter Eight 271 Answer: The promoter is located to the left (upstream) of the 3 end of the template strand. From this sequence it cannot be determined how far the promoter would be from the 5 end of the mRNA. 4. In Figure 8-9b, write a sequence that could form the hairpin loop structure. Answer: Any sequence that contains inverted complementary regions separated by a noncomplementary one would form a hairpin. One sequence would be: ACGCAAGCUUACCGAUUAUUGUAAGCUUGAAG The two bold-faced sequences would pair and form a hairpin. The intervening non-bold sequence would be the loop. 5. How do you know that the events in Figure 8-13 are occurring in the nucleus? Answer: The figure shows a double-stranded DNA molecule from which RNA is being transcribed. -
"The" Genetic Code?
Evolutionary Anthropology 14:6–11 (2005) CROTCHETS & QUIDDITIES “The” Genetic Code? KENNETH M. WEISS AND ANNE V. BUCHANAN The DNA-based code for protein through messenger and transfer RNA is widely themselves, that carry the informa- regarded as the code of life. But genomes are littered with other kinds of coding tion. elements as well, and all of them probably came after a supercode for the tRNA Your life depends on the fidelity of system itself. these many codes. Aberrant codes re- lated to cell behavior can lead to dys- genesis or various metabolic diseases. Evolution and the diversification of Everyone knows of “the” genetic Anomalous cell-surface proteins can organisms are made possible by code, by which nucleotide triplets in cause autoimmune destruction, and vi- codes, or arbitrary assignments of DNA in the nucleus of cells specify the ruses are the Alan Turings of life that “meaning,” in multiple ways. Many amino acid (aa) sequence of proteins. evolve ways to break their receptor are not widely appreciated. Codes al- This is the code described in text- codes to gain illicit entry into cells (Fig. low the same system of components books as the heart of the genetic the- 1). to be used for multiple purposes. ory of life and its evolution. Discover- But there is an additional code, a These can be open-ended, the way the ies in recent years have made things code of codes, that makes all of this alphabet and vocabulary make this more complicated by showing that ge- possible, including “the” genetic code column possible, but the flexibility of nomes are littered with all sorts of itself, and may be the oldest and most a code can become constrained once a other kinds of coding elements. -
Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases
viruses Review Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases Valentina Poletti 1,2,3,* and Fulvio Mavilio 4 1 Department of Woman and Child Health, University of Padua, 35128 Padua, Italy 2 Harvard Medical School, Harvard University, Boston, MA 02115, USA 3 Pediatric Research Institute City of Hope, 35128 Padua, Italy 4 Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy; [email protected] * Correspondence: [email protected] Abstract: Lentiviral vectors are the most frequently used tool to stably transfer and express genes in the context of gene therapy for monogenic diseases. The vast majority of clinical applications involves an ex vivo modality whereby lentiviral vectors are used to transduce autologous somatic cells, ob- tained from patients and re-delivered to patients after transduction. Examples are hematopoietic stem cells used in gene therapy for hematological or neurometabolic diseases or T cells for immunotherapy of cancer. We review the design and use of lentiviral vectors in gene therapy of monogenic diseases, with a focus on controlling gene expression by transcriptional or post-transcriptional mechanisms in the context of vectors that have already entered a clinical development phase. Keywords: lentiviral vectors; transcriptional regulation; post-transcriptional regulation; miRNA; promoters; retroviral integration; ex vivo gene therapy Citation: Poletti, V.; Mavilio, F. 1. Introduction Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases. -
Analysis of Codon Usage Patterns in Giardia Duodenalis Based on Transcriptome Data from Giardiadb
G C A T T A C G G C A T genes Article Analysis of Codon Usage Patterns in Giardia duodenalis Based on Transcriptome Data from GiardiaDB Xin Li, Xiaocen Wang, Pengtao Gong, Nan Zhang, Xichen Zhang and Jianhua Li * Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China; [email protected] (X.L.); [email protected] (X.W.); [email protected] (P.G.); [email protected] (N.Z.); [email protected] (X.Z.) * Correspondence: [email protected]; Tel.: +86-431-8783-6172; Fax: +86-431-8798-1351 Abstract: Giardia duodenalis, a flagellated parasitic protozoan, the most common cause of parasite- induced diarrheal diseases worldwide. Codon usage bias (CUB) is an important evolutionary character in most species. However, G. duodenalis CUB remains unclear. Thus, this study analyzes codon usage patterns to assess the restriction factors and obtain useful information in shaping G. duo- denalis CUB. The neutrality analysis result indicates that G. duodenalis has a wide GC3 distribution, which significantly correlates with GC12. ENC-plot result—suggesting that most genes were close to the expected curve with only a few strayed away points. This indicates that mutational pressure and natural selection played an important role in the development of CUB. The Parity Rule 2 plot (PR2) result demonstrates that the usage of GC and AT was out of proportion. Interestingly, we identified 26 optimal codons in the G. duodenalis genome, ending with G or C. In addition, GC content, gene expression, and protein size also influence G. -
Transcription and Open Reading Frame
Transcription The expression of genetic information stored in the DNA sequence starts with synthesis of the RNA copy of the gene in a process called transcription. The RNA copy of the gene is called messenger RNA (mRNA). A special enzyme, RNA polymerase, recognizes a sequence, called promoter, on the DNA double helix upstream from the protein coding sequence. RNA polymerase binds to the promoter and opens it up: separates the complementary strands at about 12-nt-long region of the promoter. Then the enzyme starts the mRNA synthesis using all 4 NTPs. The DNA strand, which is used as a template by RNA polymerase, is called the template or antisense strand. The opposite strand of the gene, which sequence is identical to the sequence of mRNA (except the substitution T U, of course), is called the coding or sense strand. There is also a special sequence after the end of the gene, which signals to RNA polymerase to terminate the mRNA synthesis. Thus synthesized mRNA molecule, which includes the protein coding region flanked by short unrelated sequences from both sides, is either translated by the ribosome into the protein molecule at the spot (in case of prokaryotes) or is transported from the nucleus to the cytoplasm (in case of eukaryotes) and there it is translated by the ribosome. Open Reading Frame (ORF) Since the genetic code is triplet, three reading frames are possible for the same mRNA molecule. For instance, the sequence: …..AUUGCCUAACCCUUAGGG…. can be separated into triplets by three possible ways: ….AUUGCCUAACCCUUAGGG…. ….AUUGCCUAACCCUUAGGG…. ….AUUGCCUAACCCUUAGGG…. The frame, in which no stop codons are encountered, is called the Open Reading Frame (ORF). -
LESSON 4 Using Bioinformatics to Analyze Protein Sequences
LESSON 4 Using Bioinformatics to 4 Analyze Protein Sequences Introduction In this lesson, students perform a paper exercise designed to reinforce the student understanding of the complementary nature of DNA and how that complementarity leads to six potential protein reading frames in any given DNA sequence. They also gain familiarity with the circular format codon table. Students then use the bioinformatics tool ORF Finder to identify the reading frames in their DNA sequence from Lesson Two and Lesson Three, and to select Class Time the proper open reading frame to use in a multiple sequence alignment with 2 class periods (approximately 50 their protein sequences. In Lesson Four, students also learn how biological minutes each). anthropologists might use bioinformatics tools in their career. Prior Knowledge Needed • DNA contains the genetic information Learning Objectives that encodes traits. • DNA is double stranded and At the end of this lesson, students will know that: anti-parallel. • Each DNA molecule is composed of two complementary strands, which are • The beginning of a DNA strand is arranged anti-parallel to one another. called the 5’ (“five prime”) region and • There are three potential reading frames on each strand of DNA, and a total the end of a DNA strand is called the of six potential reading frames for protein translation in any given region of 3’ (“three prime”) region. the DNA molecule (three on each strand). • Proteins are produced through the processes of transcription and At the end of this lesson, students will be able to: translation. • Amino acids are encoded by • Identify the best open reading frame among the six possible reading frames nucleotide triplets called codons. -
Base Paring Rules for Transcription
Base Paring Rules For Transcription Jerry window-shop his Jon traversings unduly or shortly after Giff vacillated and nerves turbulently, Silvanintoxicated labialised and camouflaged. unofficially if attentionalSynchronistic Martin Moore compel twigging, or puzzling. his clapboard curses leasing grindingly. Since the template strand will contain base pairs that bond precisely with the. Dna Base Pair Worksheet Teachers Pay Teachers. Most images show 17 base pairs The coding strand turns gray page then disappears leaving the template strand see strands above Anti-codons in the template. DNA Base Pairing Worksheet 1 CGTAAGCGCTAATTA 2. One strand whereas the DNA duplex the template strand is transcribed into a segment of mRNA shown according to the prior base-pairing rules used in DNA. As surgery the damage of DNA replication base-pairing rules apply However. Base pairs refer them the sets of hydrogen-linked nucleobases that window up nucleic acids DNA and RNA. Students begin by replicating a DNA strand and transcribing the DNA strand into RNA Then they create base pairing rules and search the. Topic 27 DNA Replication Transcription and Translation. Transcribe the DNA strand until the complementary base pairs. Therefore translation of the messenger RNA transcribed from this mutant. DNA RNA Transcription and Translation Protein Synthesis. The base-pairing rules summarize which The template strand despite the DNA contains the gene and is being transcribed pairs of nucleotides are complementary. Transcription Translation & Protein Synthesis Gene. The cell's DNA contains the instructions for carrying out the work of border cell. Rules of Base Pairing A with T the purine adenine A always pairs with the pyrimidine thymine T C with G the pyrimidine cytosine C always.