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Basic Molecular Biology

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Presentation on theme: "Basic Molecular Biology"— Presentation transcript:

1 Basic Molecular Biology
(Borrowed from “An Introduction to Bioinformatics Algorithms” by Neil C. Jones and Pavel A. Pevzner and further modified by Prof. Natalio Krasnogor) Basic Molecular Biology

2 All living things are made of Cells Cell Signaling
Outline For Section 1: All living things are made of Cells Prokaryote, Eukaryote Cell Signaling What is Inside the cell: From DNA, to RNA, to Proteins

3 Cells Hard Fact! No pre-medieval fairy tales like ID, Adam&Eve, etc For more information: “The Major Transitions in Evolution” by M. Smith and E. Szathmary Fundamental working units of every living system. Every organism is composed of one of two radically different types of cells: prokaryotic cells or eukaryotic cells. Prokaryotes and Eukaryotes are descended from the same primitive cell. All extant prokaryotic and eukaryotic cells are the result of a total of 3.5 billion years of evolution by natural selection. Crowded slide Organism of life…. Cells

4 Cells 70% water 7% small molecules 23% macromolecules
Chemical composition-by weight 70% water 7% small molecules salts Lipids amino acids nucleotides 23% macromolecules Proteins Polysaccharides lipids

5 Life begins with Cell A cell is the smallest structural unit of an organism that is capable of sustained independent functioning All cells have some common features What is Life? Can we create it in the lab? Read: The imitation game—a computational chemical approach to recognizing life. Nature Biotechnology, 24: , 2006

6 2 types of cells: Prokaryotes & Eukaryotes
Reverse sides Delete continues

7 All Cells have common Cycles
Born, eat, replicate, and die

8 Prokaryotes and Eukaryotes
According to the most recent evidence, there are three main branches to the tree of life. Prokaryotes include Archaea (“ancient ones”) and bacteria. Eukaryotes are kingdom Eukarya and includes plants, animals, fungi and certain algae.

9 Prokaryotes and Eukaryotes, continued
Single cell Single or multi cell No nucleus Nucleus No organelles Organelles One piece of circular DNA (plasmid) Chromosomes No mRNA post transcriptional modification Exons/Introns splicing

10 Prokaryotes v.s. Eukaryotes Structural differences
Eubacterial (blue green algae) and archaebacteria only one type of membrane-- plasma membrane forms the boundary of the cell proper The smallest cells known are bacteria Ecoli cell 3x106 protein molecules polypeptide species. Eukaryotes plants, animals, Protista, and fungi complex systems of internal membranes forms organelle and compartments The volume of the cell is several hundred times larger Hela cell 5x109 protein molecules ,000 polypeptide species Structural differences Two columns labelled prokaryotes and eukaryotes

11 Signaling Pathways: Control Gene Activity
Instead of having brains, cells make decisions through complex networks of chemical reactions, called pathways Synthesize new materials Break other materials down for spare parts Signal to eat, die, reproduce, sporulate, etc Even Bacteria are smart entities. Read: Bacteria Harnessing Complexity by E. Ben-Jacob and colleagues

12 Example of cell signaling

13 Cells Information and Machinery
Cells store all information to replicate itself Human genome is around 3 billions base pairs long Almost every cell in human body contains same set of genes But not all genes are used or expressed by those cells Machinery: Collect and manufacture components Carry out replication Kick-start its new offspring (A cell is like a car factory but FAR more complex and efficient)

14 Overview of organizations of life
Nucleus = library Chromosomes = bookshelves Genes = books Almost every cell in an organism contains the same libraries and the same sets of books. Books represent all the information (DNA) that every cell in the body needs so it can grow and carry out its various functions. Moreover, more recent discoveries suggest that the books, bookshelves and libraries are not passive waiting to be read but are, sometimes, rewriting and rewiring themselves!

15 Terminology a bacteria contains about 600,000 DNA base pairs
The genome is an organism’s complete set of DNA. a bacteria contains about 600,000 DNA base pairs human and mouse genomes have some 3 billion. human genome has 23 distinct chromosomes. Each chromosome contains many genes. Gene basic physical and functional units of heredity. specific sequences of DNA bases that encode instructions on how and when to make proteins. Proteins Make up the cellular structure large, complex molecules made up of smaller subunits called amino acids.

16 All Life depends on 3 critical molecules
DNAs Hold information on how cell works RNAs Act to transfer short pieces of information to different parts of cell Provide templates to synthesize into protein Proteins Form enzymes that send signals to other cells and regulate gene activity Form body’s major components (e.g. hair, skin, etc.) Are life’s laborers! Computationally, all three can be represented as sequences of a certain 4-letter (DNA/RNA) or 20-letter (Proteins) alphabet

17 DNA, RNA, and the Flow of Information
Replication Transcription Translation Weismann Barrier / Central Dogma of Molecular Biology

18 Overview of DNA to RNA to Protein
A gene is expressed in two steps Transcription: RNA synthesis Translation: Protein synthesis

19 DNA: The Basis of Life Deoxyribonucleic Acid (DNA) DNA is a polymer
Double stranded with complementary strands A-T, C-G DNA is a polymer Sugar-Phosphate-Base Bases held together by H bonding to the opposite strand

20 RNA RNA is similar to DNA chemically. It is usually only a single strand. T(hyamine) is replaced by U(racil) Some forms of RNA can form secondary structures by“pairing up” with itself. This can have impact on its properties dramatically. DNA and RNA can pair with each other. tRNA linear and 3D view:

21 RNA, continued Several types exist, classified by function:
hnRNA (heterogeneous nuclear RNA): Eukaryotic mRNA primary transcipts with introns that have not yet been excised (pre-mRNA). mRNA: this is what is usually being referred to when a Bioinformatician says “RNA”. This is used to carry a gene’s message out of the nucleus. tRNA: transfers genetic information from mRNA to an amino acid sequence as to build a protein rRNA: ribosomal RNA. Part of the ribosome which is involved in translation.

22 Transcription Transcription is highly regulated. Most DNA is in a dense form where it cannot be transcribed. To start, transcription requires a promoter, a small specific sequence of DNA to which polymerase can bind (~40 base pairs “upstream” of gene) Finding these promoter regions is only a partially solved problem that is related to motif finding. There can also be repressors and inhibitors acting in various ways to stop transcription. This makes regulation of gene transcription complex to understand.

23 Definition of a Gene Regulatory regions: up to 50 kb upstream of +1 site Exons: protein coding and untranslated regions (UTR) 1 to 178 exons per gene (mean 8.8) 8 bp to 17 kb per exon (mean 145 bp) Introns: splice acceptor and donor sites, junk DNA average 1 kb – 50 kb per intron Gene size: Largest – 2.4 Mb (Dystrophin). Mean – 27 kb.

24 Splicing

25 Splicing and other RNA processing
In Eukaryotic cells, RNA is processed between transcription and translation. This complicates the relationship between a DNA gene and the protein it codes for. Sometimes alternate RNA processing can lead to an alternate protein (splice variants) as a result. This is true in the immune system.

26 Proteins: Crucial molecules for the functioning of life
Structural Proteins: the organism's basic building blocks, eg. collagen, nails, hair, etc. Enzymes: biological engines which mediate multitude of biochemical reactions. Usually enzymes are very specific and catalyze only a single type of reaction, but they can play a role in more than one pathway. Transmembrane proteins: they are the cell’s housekeepers, eg. By regulating cell volume, extraction and concentration of small molecules from the extracellular environment and generation of ionic gradients essential for muscle and nerve cell function (sodium/potasium pump is an example) Proteins are polypeptide chains, constructed by joining a certain kind of peptides, amino acids, in a linear way The chain of amino acids, however folds to create very complex 3D structures

27 Translation The process of going from RNA to polypeptide.
Three base pairs of RNA (called a codon) correspond to one amino acid based on a fixed table. Always starts with Methionine and ends with a stop codon

28 Amino Acids

29 Protein Structure: Introduction
Different amino acids have different properties These properties will affect the protein structure and function Hydrophobicity, for instance, is the main driving force (but not the only one) of the folding process

30 Protein Structure: Hierarchical nature of protein structure
Primary Structure = Sequence of amino acids MKYNNHDKIRDFIIIEAYMFRFKKKVKPEVDMTIKEFILLTYLFHQQENTLPFKKIVSDLCYKQSDLVQHIKVLVKHSYISKVRSKIDERNTYISISEEQREKIAERVTLFDQIIKQFNLADQSESQMIPKDSKEFLNLMMYTMYFKNIIKKHLTLSFVEFTILAIITSQNKNIVLLKDLIETIHHKYPQTVRALNNLKKQGYLIKERSTEDERKILIHMDDAQQDHAEQLLAQVNQLLADKDHLHLVFE Secondary Structure Tertiary Local Interactions Global Interactions

31 Protein Structure: Why is structure important?
The function of a protein depends greatly on its structure The structure that a protein adopts is vital to it’s chemistry Its structure determines which of its amino acids are exposed to carry out the protein’s function Its structure also determines what substrates it can react with

32 Protein Structure: Mostly lacking information
Therefore, it is clear that knowing the structure of a protein is crucial for many tasks However, we only know the structure for a very small fraction of all the proteins that we are aware of The UniProtKB/TrEMBL archive contains ( ) sequences The PDB archive of protein structure contains only 84223(76669) structures In the native state, proteins fold on its own as soon as they are generated, amino-acid by amino-acid (with few exceptions e.g. chaperones)  can we predict this process as to close the gap between protein sequences and their 3D structures?

33 Central Dogma of Biology: A Bioinformatics Perspective
The information for making proteins is stored in DNA. There is a process (transcription and translation) by which DNA is converted to protein. By understanding this process and how it is regulated we can make predictions and models of cells. Assembly Protein Sequence/Structure Analysis Sequence analysis Gene Finding Computational Problems


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