An Introductory Course Lecture 3 5 Cell Biology Introduction to Cell Biology Dr Oluwatosin Oluwadare August 31 2020 Computational Biology amp Bioinformatics 2 Molecular Biology Cell is the unit of structure and function of all living things ID: 912621
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BIOINFORMATICS & COMPUTATIONAL BIOLOGY(An Introductory Course)
Lecture 3
- 5:
Cell Biology
Slide2Introduction to Cell BiologyDr. Oluwatosin Oluwadare
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Slide3Molecular BiologyCell is the unit of structure and function of all living things.Two classes of organismProkaryotesBacteriaArchaeaEukaryotes Plant
AnimalFungi
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Slide4ProkaryotesNo one knew bacteria, or any other cell existed until Antonie van Leeuwenheok made the first high-resolution microscope in 1660.All prokaryotes have the same basic anatomy consisting of:A cell membrane
CytoplasmA circular DNA chromosome
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Bacterial Cell Anatomy and Internal Structure. Jack0m/Getty Images
Slide5Prokaryotes vs. EukaryotesProkaryotes: Lack nucleus and internal OrganellesThey are simple, more commonly known as bacteria Eukaryotes(meaning “true nucleus”) They are much complex than the prokaryotes
They have many membrane bounded organelles and large genome
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Slide6Prokaryotes vs. Eukaryoteshttps://youtu.be/9o6huiw7u5o
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Slide7Central Dogma of BiologyAn illustration showing the flow of information between DNA, RNA and protein.
A three-step organization of DNA to RNA to Protein
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Image credit: Genome Research Limited
Slide8Central Dogma of BiologyThe central dogma of molecular biology explains the flow of genetic information, from DNA to RNA
, to make a functional product, a Protein
.DNA is a collection of blueprints, or genes that store the information to make proteins.
The process by which the DNA instructions are converted into the functional product is called gene expression.
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Slide9Gene Expression Gene expression has two key stages:TranscriptionTranslationTranscription: The coded information in the DNA of every cell is converted into small RNA messages
Translation: The messages are read and are used to synthesize specific proteins.
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Slide10Central Dogma of Biology-Reverse TranscriptionAugust 31, 2020
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Reverse
TranscriptionRNA → DNA(HIV Virus)
Slide11A New Genetic Order
An Analogy of this organization
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Carpentry shop office
Carpentry shop
Slide12DNA (Deoxyribonucleic Acid )A cell’s DNA holds a library describing how the cell works.DNA is a linear sequence of four different types of nucleotides. A is for Adenine G is for Guanine T is for Thymine
C is for Cytosine They pair A-T and C-G on complimentary strands(Jones and Pevzner, 2004)
CGAATGGGAAA……August 31, 2020
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Slide13DNA (Deoxyribose Nucleotide Acids)August 31, 2020
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Slide14DNA (Deoxyribonucleic Acid )August 31, 2020Computational Biology & Bioinformatics
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Slide15RNA (Ribonucleic Acid)Ribonucleic acid (RNA) is a molecule similar to DNA. Unlike DNA,
RNA is single-stranded.An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups.
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Slide16RNA (Ribonucleic Acid)Attached to each sugar is one of four bases-Adenine (A)Uracil (U) (Replaces Thymine in DNA)Cytosine (C)guanine (G).
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Slide17NucleotideA nucleotide is the basic building block of nucleic acids. RNA and DNA are polymers made of long chains of nucleotides. A Nucleotide consists of a sugar molecule
(either ribose in RNA or deoxyribose in DNA) attached to a
phosphate group and a nitrogen-containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G), and thymine (T). In RNA, the base uracil (U) takes the place of thymine.
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Slide20Nucleotide
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Slide215’ and 3’ end of a DNAThe strands of DNA run anti-parallel, or in opposite directions: the 5’ end of one strand is paired with the 3’ end of the other. They are used to signify the directionality of a DNA strand.
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Source: Dr. Gary Stormo, 2002
Slide225’ and 3’ end of a DNAVideo Explanationhttps://youtu.be/qWZYpHSXvJo
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Computer Model of a DNA
Slide235’ and 3’ end of a DNAIn the context of DNA A always pairs with T, and G with C.Therefore, if the sequence of one strand of DNA is known, the sequence of the other strand can be determined as well.Questions? If one strand of DNA is known to have the sequence 5’-ATGGCT-3’, the other strand must have the sequence equals
3’-TACCGA-5’.
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Slide245’ and 3’ end of a DNAAugust 31, 2020Computational Biology & Bioinformatics
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Slide25The NucleusDr. Oluwatosin Oluwadare
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Slide26Eukaryotes- The NucleusAugust 31, 2020Computational Biology & Bioinformatics
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Slide27The Nucleus-ChromosomeThe Nucleus houses the chromosomes and all the enzymes necessary to replicate, transcribe, and repair genes.Each chromosome is a single, extremely long DNA molecule.
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Slide28The Nucleus - DNAThe DNA is a double stranded nucleic acid that encodes genes, and is constructed from four deoxynucleotides.Hence the name deoxynucleic acid (DNA).Two DNA strands coil around each-other like strands in a piece of rope. For this reason it is known as the double helix.
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Slide29The Nucleus - GenesGenes store the information to make Proteins.The Proteins are used to construct the cell, and a special group of them, called the enzyme control the chemical reactions that necessary for the cells to live.
Human genes is between 20,000 to 25,000The genome is split into 46 chromosomes, 23 from father and 23 from mother.
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Slide30The Nucleus – DNA Packaging A haploid human genome contains approximately 3 billion base pairs of DNA packaged into 23 chromosomes. Most cells in the body are diploid except the for female ova and male spermA diploid cell contains 23 pairs of chromosomes resulting in 6 billion base pairs per cell.
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Slide31The Nucleus – DNA Packaging Each base pair is around 0.34 nanometers long (a nanometer is one-billionth of a meter).Each diploid cell, therefore, contains about 2 meters of DNA [(0.34 × 10-9) × (6 × 109)].
By estimate the human body contains about 50 trillion cells, hence, by calculation we have about 100 trillion meters of DNA per human/person.
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Slide32The Nucleus – DNA Packaging
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Slide33Micron is another name for micrometer1 micron = 10−6The Nucleus is typically only 2 to 10 microns in diameter. (Fawcett, D. W. (1981))In mammalian cells, the average diameter of the nucleus is approximately
6 microns(µm). (Alberts, B (2002))
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The Nucleus – DNA Packaging
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How do you fit in a 2-meter long DNA thread into a 6-micron nucleus?Answer: HistonesTo reduce the length of this long genetic threads, chromosomes are wrapped around special proteins called
histonesThese proteins are added to DNA to make it more compact.
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Slide36The Nucleus – DNA Packaging Five major families of histones exist:H1, H2A, H2B, H3, and H4 Histones are small positively charged protein(Lehninger, A.L. et al., 2005, Van Holde, 1988)
Histones H2A, H2B, H3 and H4 are known as the core histones.Histones H1/H5 are known as the linker histones.
DNA is negatively charged, due to the phosphate groups in its phosphate-sugar backbone, so histones bind with DNA very tightly.
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Slide37The Nucleus – DNA Packaging The complex of DNA and protein, histones, is called Chromatin.The basic repeating unit of eukaryotic chromatin is the NucleosomeA single nucleosome consists of about 146-150 base pairs of DNA sequence wrapped around a core of histone proteins, histone
octomer. Eight histones proteins form a spherical structure called a histone octomer
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Slide38The Nucleus – DNA Packaging The spherical structure of the nucleosome makes the relaxed chromosome look like a string of beadsTwo each of the histones H2A, H2B, H3, and H4 come together to form a histone octamer, which binds and wraps approximately 1.7 turns of DNA, or about 146 base pairs.
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David O Morgan - The Cell Cycle. Principles of Control.
Slide39The Nucleus – DNA Packaging Every chromosome contains hundreds of thousands of nucleosomes, and these nucleosomes are joined by the DNA that runs between them (an average of about 20 base pairs). This joining DNA is referred to as linker DNA.
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Slide40The Nucleus – DNA Packaging Chromatin Is Coiled into Higher-Order StructuresChromatin Condensation/CompactionThe packaging of DNA into nucleosomes shortens the fiber length about sevenfold. Consider 2-meter, 200cm long, DNA will become a "string-of-beads" chromatin fiber just 28 cm long
.However, the chromatin is still too long to fit into the nucleus.
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Slide41The Nucleus – DNA Packaging Therefore, chromatin is further coiled into an even shorter, thicker fiber, termed the "30-nanometer fiber," because it is approximately 30 nanometers in diameter Following this arrangement, the chromosome contracts to form a compact structure that is 10,000 times shorter than the bare piece of DNA.
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Slide42The Nucleus – DNA Packaging August 31, 2020Computational Biology & Bioinformatics
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Slide43Simple IllustrationAugust 31, 2020Computational Biology & Bioinformatics
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Slide45DNA TranscriptionDr. Oluwatosin OluwadareAugust 31, 2020
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Slide46DNA TranscriptionThe instructions stored within DNA are read and processed by a cell in two steps: (Remember Gene expression) Transcription Translation
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Slide47A New Genetic OrderAn Analogy of this organizationAugust 31, 2020
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Slide48A New Genetic OrderA cell’s DNA holds thousands of information describing how the cell worksRNA acts to transfer short pieces of information to different places in the cell.In the cell, a working copy of the gene is a molecule called messenger RNA or mRNA.It carries the information stored in DNA to other areas of the cell.
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Slide49Transcription of Gene into RNA: How does it Occur?DNA --> transcription --> RNAA portion of the cell's DNA serves as a template for creation of an RNA molecule. So if the DNA is double helix, why do you need only a portion to serve as a template for the RNA molecule creation?
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Slide50Transcription of Gene into RNAInitiation and Stand ElongationTranscription begins when an enzyme called RNA polymerase attaches to the DNA template strand and begins assembling a new chain of nucleotides to produce a complementary RNA strand.RNA polymerase binds to the DNA in the specific area that supports transcription called
promoter region.The enzyme reads the parental DNA in the 3’ to 5’ direction and creates a RNA strand that grows in the 5’ to 3’ direction.
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Slide51Transcription of Gene into RNATermination Termination occurs as soon as the polymerase reaches a specific series of nucleotides along the DNA template.This sequence is called the termination sequenceOnce termination is complete, the mRNA molecule falls off the DNA template.
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Slide52TranscriptionAugust 31, 2020
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Slide53Transcription of Gene into RNAAugust 31, 2020Computational Biology & Bioinformatics
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Slide54Different Kinds of RNAmRNA: messager RNAcarry genetic information out of nucleus for protein synthesis (transcription process: RNA polymerase)rRNA: ribosomal RNAconstitute 50% of ribosome, which is a molecular assembly for protein synthesis
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Slide55Different Kinds of RNAtRNA: transfer RNAdecode information (map 3 nucleotides to amino acid); transfer amino acidsnRNA: small nuclear RNA are required for splicing; molecules found in nucleus involve RNA splicing
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Slide56A Video Explanationhttps://www.youtube.com/watch?v=DKgJPhvCDU8August 31, 2020
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Slide57Translation Dr. Oluwatosin OluwadareAugust 31, 2020
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Slide58TranslationThe instructions stored within DNA are read and processed by a cell in two steps: (Remember Gene expression) Transcription Translation
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Slide59A New Genetic OrderAn Analogy of this organizationAugust 31, 2020
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Slide60Translation: ProteinsRNA --> translation --> proteinRNA, smaller volumes of information are used as templates, to synthesize proteins.Proteins are an important class of molecules found in all living cells.
A protein is composed of one or more long chains of amino acids, the sequence of which corresponds to the DNA sequence of the gene
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Slide61Unit of Protein: Amino Acid
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Slide62Genetic Code and TranslationThree Nucleotides is called a codon
Codons are linked together to form a long continuous sequence that is called a
geneCodons code for amino acid.It is worth-noting that, not all the codons code for amino acid.
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Slide64Genetic Code and TranslationAugust 31, 2020Computational Biology & Bioinformatics
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Slide65The Universal Genetic CodeAll living things on things consist of 64 codons that specify 20 amino acids and the start and stop sites.The sequence TGA signal in a DNA, denoted as UGA in a RNA specifies the end of the gene.
The special codon ATG in a DNA, denoted as UTG signals the start site
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Slide66Amino Acid StructureAugust 31, 2020Computational Biology & Bioinformatics
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Slide67Amino Acid forms PeptideAugust 31, 2020Computational Biology & Bioinformatics
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Slide68Peptide bondPolypeptides and proteins are chains of amino acids held together by peptide bondsAugust 31, 2020
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Slide69Protein SequenceAugust 31, 2020Computational Biology & Bioinformatics
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N-terminal
C-terminal
…
Amino Acid 1
Amino Acid 2
Peptide bond
Has orientations from N-terminal to C-terminal
Slide70Protein StructureThe linear sequence of Amino Acids folds to form a complex 3D structureThe structural organization of the protein affects its functions
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Slide71Central Dogma of ProteomicsSequences (Protein) and structures
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AGCWY……
Cell
Sequences (Protein)
Structure
Function
Slide72Protein structure predictionJPredProtein Structure Prediction3D structure of pepsin (PDB ID: 1PSN)>1PSN:A|PDBID|CHAIN|SEQUENCEVDEQPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSLACTNHNRFNPEDSSTYQSTSETVSITYGTGSMTGILGYDTVQVGGISDTNQIFGLSETEPGSFLYYAPFDGILGLAYPSISSSGATPVFDNIWNQGLVSQDLFSVYLSADDQSGSVVIFGGIDSSYYTGSLNWVPVTVEGYWQITVDSITMNGEAIACAEGCQAIVDTGTSLLTGPTSPIANIQSDIGASENSDGDMVVSCSAISSLPDIVFTINGVQYPVPPSAYILQSEGSCISGFQGMNLPTESGELWILGDVFIRQYFTVFDRANNQVGLAPVA
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Slide73Levels of Protein OrganizationPrimary protein structure:Is sequence of a chain of amino acids/residues
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Residue1
Residue2
Slide74Levels of Protein OrganizationSecondary Structure (helix, strand, coil)It occurs when the sequence of amino acid are linked by hydrogen bonds
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Alpha Helix Beta Strand / Sheet Coil
Slide75Levels of Protein OrganizationTertiary Structure It occurs when certain attractions are present between alpha helix and Beta SheetProtein tertiary structure is the three- dimensional shape of a protein
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Slide76Protein FunctionProteins play a variety of roles in the cell, including:structural (cytoskeleton), mechanical (muscle),biochemical (enzymes), and cell signaling (hormones)
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Slide77Protein FunctionEnzymatic catalysisTransport and storageCoordinated motionImmune protectionGeneration and transmission of nerve impulsesControl of growth and differentiationStructural materials
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Slide78Levels of Protein OrganizationQuaternary Structure (complex) Protein consisting of more than one amino acid chain.
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G Protein Complex
Slide79ProteinsMany genes in the genome code for proteins.There are thousands and thousands of proteins that your cells and body makes every single day. In the human genome, there are approximately 20,000 genes that code for proteins.
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Slide80Genome It is the complete set of DNA, including all of its genes, for an organism.Each genome contains all of the information needed to build and maintain that organism.Currently, we do not know what a substantial amount of the genomes do. Are they really “junk”? (we do not yet understand)
It is divided into other components called chromosomes synonymous to “chapters of a book”
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Slide81Complexity of the GenomeOverall, the complexity of a Eukaryotes, compared with Prokaryotes, suggest the reason for a larger genomeBacteria usually have 2,000- 4,000 genesHuman genome is estimated 20,000- 25,000
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Slide82ChromosomeEukaryotes split their genome into several linear chromosomes.A chromosome is an organized package of DNA found in the nucleus of the cell. Different organisms have different numbers of chromosomes. It contains genes as well as Unused DNA sometimes called “Junk DNA”
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Slide83GeneThe gene is the basic physical unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify traits
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Slide84GeneIt is a sequence of nucleotides in DNA or RNA that encodes the synthesis of a gene product, either RNA or protein.
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Image Credit:
Wikimedia Commons; User – Plociam
Slide85Organisms and Genes
Organism
ChromosomesBasesGenes
Homo sapiens (human)463.2 billion20,000 – 25,000
Drosophila melanogaster (fruit fly)8180 million13,000 – 14,000Caenorhabditis elegans (microscopic roundworm)
12
97 million
~20,000
Canis
familiaris
(domestic dog)
78
2.4 billion
~20,000
Saccharomyces cerevisiae
(budding yeast)
32
12 million
~7,000
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Slide86Human GenomeHuman cells, for example, have 46 chromosomes(23 pairs of chromosome)23 chromosome from the mother23 chromosomes from the father 22 pairs of numbered chromosomes, called autosomes, and one pair of sex chromosomes, X and Y
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Slide87Human Genome 46 Chromosomes: 22 pairs + Pair of Sex chromosomeMale: X + YFemale: X + X
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Slide88Human GenomeEvery Cell contains the same genomic informationExcept sperm and eggs, which only contain half the genome
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Slide89The Cell CycleDr. Oluwatosin Oluwadare
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Slide90Cell CycleMost cell spends their time cycling between a state of calm(interphase) and cell division.Interphase is further divided into three subphases: Gap 1(G1),
S Phase (DNA Synthesis/DNA Replication), and Gap 2(G2)Cells may exit the cycle by entering s special phase called G
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Slide91Cell CycleThe termination of G2 occurs with the division of the cell and the return to G1 A cell cycle is a series of events that takes place in a cell as it grows and dividesA cell spends most of its time in what is called interphase, and during this time it grows, replicates its chromosomes, and prepares for cell division.
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Slide92Cell CycleThe cell then leaves interphase, undergoes mitosis, and completes its division. The resulting cells, known as daughter cells, each enter their own interphase and begin a new round of the cell cycle.
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Slide93Cell CycleAugust 31, 2020Computational Biology & Bioinformatics
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Slide94DNA ReplicationDNA replication is the process by which a molecule of DNA is duplicated.Cell duplicate’s its genome so that each daughter cell winds up with a complete set of chromosomes after cell division
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Slide95DNA ReplicationHelicase is an enzyme responsible for separating the two DNA strands.So that DNA polymerase can synthesize new strands
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Slide96DNA ReplicationDNA Polymerase: An enzyme directly response for reading the template strand, and for constructing new daughter stand.It reads the parental DNA in the 3’ to 5’ direction and creates a daughter stand that grows in the 5’ to 3’ direction. For every replication fork, there is a leading and lagging strand:
Leading strand reads 3’ to 5’ in the direction of the forkLagging strand reads 5’ to 3’
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Genetics for Dummies, Tara Robinson
homologous chromosomes
homologous chromosomes copied
Slide99Daughter Cells and CancerNormal cells produce two daughter cells by mitotic division. Cancer cells are distinguished for their ability to produce more than two daughter cells.Three or more daughter cells may develop from dividing cancer cells and these cells are produced at a faster rate than normal cells.
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Slide100Daughter Cells and CancerDue to the irregular division of cancer cells, daughter cells may also end up with too many or not enough chromosomes.Cause: Cancer cells often develop as a result of mutations in genes that control normal cell growth or that function to suppress cancer cell formation.
Hence, These cells grow uncontrollably, exhausting the nutrients in the surrounding area.
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https://www.thoughtco.com/daughter-cells-defined-4024745?
Slide101Cell Division – Binary FissionProkaryotes all divide by a simple process called binary fission.It is a kind of asexual reproduction.In binary fission DNA replication and segregation occur simultaneously.
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Slide102Cell Division - MitosisCell Division among Eukaryotes is more complicated than it is in Prokaryotes.The biggest problem Eukaryotes face is the huge amount of genome which most be duplicated.Cell division in Eukaryotes is by Mitosis which is divided four stages:ProphaseMetaphaseAnaphase
Telophase
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Slide103Cell Division - MeiosisMeiosis is used to make special cells - sperm cells and egg cells - that have half the normal number of chromosomes. It reduces the number from 23 pairs of chromosomes to 23 single chromosomes.It is intended for sexual reproduction and occurs exclusively for ovaries and testes.
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Slide105Phases of Mitosishttps://www2.le.ac.uk/projects/vgec/schoolsandcolleges/topics/cellcycle-mitosis-meiosis
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Slide106Summary Central Dogma of Biology:A three-step organization of DNA to RNA to ProteinDNA
transcribes to RNA translates to Protein
Cell BiologyEukaryotesProkaryotesDNA: a double-stranded nucleic acid, that encodes cellular genes.Made from {A, G, C, T}It is known as double helix
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Slide107SummaryRNA: a single-stranded moleculeMade from {A, G, C, U}Types are mRNA, tRNA, rRNA, miRNAProtein: basic unit is amino acidAmino Acid are formed by CodonsHas N-terminal and C-terminalDogma: Sequence-->Structure-->Function
Gene is a unit of heredity which is transferred from a parent to offspring.It holds the blueprint of protein function in the cell.
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Slide108Referenceshttps://www.genome.gov/genetics-glossary/https://www.genome.gov/genetics-glossary/Nucleosome
Jones, N. C., Pevzner, P. A., & Pevzner, P. (2004).
An introduction to bioinformatics algorithms. MIT press.Annunziato, A. (2008) DNA Packaging: Nucleosomes and Chromatin.
Nature Education 1(1):26Alberts, B (2002). Molecular biology of the cell
(4th ed.). Garland Science. p. 197. ISBN 978-0815340720.Fawcett, D. W. (1981). The cell: its organelles and inclusions: an atlas of fine structure
(No. 576.31 FAW).
Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2005).
Lehninger principles of biochemistry
. Macmillan.
Van Holde, K. E.
Chromatin: Springer Series in Molecular Biology
(New York, Springer-Verlag, 1988)
Van Holde, K. E.,
et al
. A model for particulate structure in chromatin.
Nucleic Acids Research
1
, 1579–1586 (1974)
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Slide109ReferencesWolffe, A. P. Chromatin: Structure and Function
, 3rd ed. (San Diego, Academic, 1999)Woodcock, C. L. A milestone in the odyssey of higher-order chromatin structure.
Nature Structural and Molecular Biology 12, 639–640 (2005) (
link to article)https://www.nature.com/scitable/topicpage/the-information-in-dna-is-decoded-by-6524808https://www.genome.gov/genetics-glossary/Protein
https://www.genome.gov/genetics-glossary/GeneReece, Jane B., and Neil A. Campbell. Campbell Biology. Benjamin Cummings, 2011.Dr. Jianhua Ruan, Department of Computer Science, UTSADr. Jianlin Cheng, Deparmtment of Electrical Engineering and Computer Science, University of Missouri, Columbia https://www.thoughtco.com/daughter-cells-defined-4024745?August 31, 2020
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