Biology: The substrate of bioinformatics

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1 Bi01_1 Unit 01: Biology: The substrate of bioinformatics What is Bioinformatics? Bi01_2 handling of information related to living organisms understood on the basis of molecular biology Nature does it. We try to understand store model, represent simulate predict visualize search it... Bio- Informatics 1

2 Information is a key feature of life Bi01_3 wing of a fly: highly ordered structure, based on information high order - low entropy heap of rubbish: low order - high entropy Information is the key feature of life Bi01_4! wing of a fly: highly ordered structure, based on information heap of rubbish: Living organism: low order - entropy fighting high entropy apparatus 2

3 Living System: Entropy Fighting Apparatus Bi01_5 In order to maintain low entropy, living organisms must expend energy to keep things orderly. The functions of life, therefore, are meant to facilitate the acquisition and orderly expenditure of energy substrates, nutrition (low order) Living System: Entropy Fighting Apparatus Bi01_6 How does it work? (understanding the mechanisms of life) substrates, nutrition (low order) 3

DesoxyriboNucleic Acid Living System: Closeups 4 letter alphabeth

4 The Central Dogma Bi01_7 feedback = gene regulation genome can replicate itself transcription translation GENE Expression DesoxyriboNucleic Acid Living System: Closeups 4 letter alphabeth for nucleotides A...adenine G...guanine C...cytosine T...thymine Bi01_8 4

5 Living System: Closeups Bi01_9 Living System: Closeups Bi01_10 DNA replication 5

Living System: Closeups Bi01_11 (1998) replication transcription translation (1998) Transcription from tandemly arranged rrna genes, as visualized in the electron microscope.

The large particles at the 5' end of each rrna transcript ( lower panel) are believed to reflect the beginning of ribosome assembly; RNA polymerase molecules are also clearly visible as a series of

) transcription DNA unwinding and rewinding by RNA polymerase.

6 Living System: Closeups Bi01_11 (1998) replication transcription translation (1998) Transcription from tandemly arranged rrna genes, as visualized in the electron microscope. The pattern of alternating transcribed gene and nontranscribed spacer is readily seen in the lower-magnification view in the upper panel. The large particles at the 5' end of each rrna transcript ( lower panel) are believed to reflect the beginning of ribosome assembly; RNA polymerase molecules are also clearly visible as a series of dots along the DNA. (Upper panel, from V.E. Foe, Cold Spring Harbor Symp. Quant. Biol. 42: , 1978; lower panel, courtesy of Ulrich Scheer.) transcription DNA unwinding and rewinding by RNA polymerase. A moving RNA polymerase molecule is continuously unwinding the DNA helix ahead of the polymerization site while rewinding the two DNA strands behind this site to displace the newly formed RNA chain. A short region of DNA/RNA helix is therefore formed only transiently, and the final RNA product is released as a single-stranded copy of one of the two DNA strands. transcription, start & end Living System: Closeups Bi01_12 replication transcription translation transcription, proceeding from high Lewin resolution (2000) 6

7 transcription, start & end Living System: Closeups Bi01_13 replication transcription translation RNA polymerase Transcription and mrna Processing Bi01_14 from Lewin(2000) 7

Transcription,, Start & Stop Bi01_15 (1998) Transcriptions,, Start & Stop, Details Bi01_16 (1998) Start and stop signals for RNA synthesis by a bacterial RNA polymerase.

8 Transcription,, Start & Stop Bi01_15 (1998) Transcriptions,, Start & Stop, Details Bi01_16 (1998) Start and stop signals for RNA synthesis by a bacterial RNA polymerase. Here, the lower strand of DNA is the template strand, whereas the upper strand corresponds in sequence to the RNA that is made (note the substitution of U in RNA for T in DNA). (A) The polymerase begins transcribing at the start site. Two short sequences (shaded red), about -35 and -10 nucleotides from the start, determine where the polymerase binds; close relatives of these two hexanucleotide sequences, properly spaced from each other, specify the promoter for most E. coli genes. (B) A stop (termination) signal. The E. colirna polymerase stops when it synthesizes a run of U residues (shaded blue) from a complementary run of A residues on the template strand, provided that it has just synthesized a selfcomplementary RNA nucleotide sequence (shaded green), which rapidly forms a hairpin helix that is crucial for stopping transcription. The sequence of nucleotides in the self-complementary region can vary widely. 8

9 Transcription of multiple Genes in different directions Bi01_17 (1998) Gene looks like fragmented files on disk Bi01_18 (1998) 9

After assembly of the spliceosome, the reaction occurs in two steps: in step 1 the branch-point A nucleotide in the intron sequence, which is located close to the 3' splice site, attacks the 5'

10 1 st st Copy whole stuff, then cut out introns (splicing) Bi01_19 (1998) Splicing,, Details Bi01_20 (1998) The RNA splicing mechanism. RNA splicing is catalyzed by a spliceosome formed from the assembly of U1, U2, U5, and U4/U6 snrnps (shown as green circles) plus other components (not shown). After assembly of the spliceosome, the reaction occurs in two steps: in step 1 the branch-point A nucleotide in the intron sequence, which is located close to the 3' splice site, attacks the 5' splice site and cleaves it; the cut 5' end of the intron sequence thereby becomes covalently linked to this A nucleotide, forming the branched nucleotide shown in Figure In step 2 the 3'-OH end of the first exon sequence, which was created in the first step, adds to the beginning of the second exon sequence, cleaving the RNA molecule at the 3' splice site; the two exon sequences are thereby joined to each other and the intron sequence is released as a lariat. The spliceosome complex sediments at 60S, indicating that it is nearly as large as a ribosome. These splicing reactions occur in the nucleus and generate mrna molecules from primary RNA transcripts (mrna precursor molecules). 10

acting as a catalyst for copying processes of various types: RNA RNA RNA protein) Role 1: RNA as a template for

11 Different Roles of RNA Bi01_21 RiboNucleic Acid 4 letter alphabeth Adenine Guanine Cytosine Uracil (instead of T in DNA) acting as a template (source of information) for synthesis of a complementary strand synthesis of a protein (mrna) acting as a catalyst for copying processes of various types: RNA RNA RNA protein) Role 1: RNA as a template for RNA-synthesis Bi01_22 (1994) Relevant aspects: Carrying of information passing on information encoded in nucleotide sequence (1994) 11

12 Exhibitionist RNA: shows its body Bi01_23 (1994) binding preferences A-U & C-G induce bindings within RNA-molecule and a 3D-shape Bi01_24 Role 2: RNA as catalyst (1994) 12

Fully advanced role of trna as a catalyst: 3D

all that (translation) occurs selective binding to

13 Fully advanced role of trna as a catalyst: 3D structures and selective binding capability of trna Bi01_25 selective binding to amino acid information the protein machinery housing where all that (translation) occurs selective binding to mrna Special RNA Structure helps Splicing Bi01_26 from Lewin(2000) 13

14 Roles of RNA in evolution of life (in a nutshell) Bi01_27 An RNA molecule therefore has two special characteristics: it carries information encoded in its nucleotide sequence that it can pass on by the process of replication, and it has a specific folded structure that enables it to interact selectively with other molecules and determines how it will respond to the ambient conditions. These two features - one informational, the other functional - are the two properties essential for evolution. The nucleotide sequence of an RNA molecule is analogous to the genotype - the hereditary information - of an organism. The folded three-dimensional structure is analogous to the phenotype - the expression of the genetic information on which natural selection operates. (1994) Folded RNA scetch Living System: Closeups Bi01_28 replication transcription translation RiboNucleic Acid 4 letter alphabeth Adenine Guanine Cytosine Uracil (instead of T in DNA) 20 letter alphabeth why? 14

Bi01_29 Proteins are chains of amino acids (Polypeptides) from Brown (1999) DNA replication RNA transcription PROTEIN translation Bi01_30 Proteine sind Polypeptide Aminosäure DNA Molmasse Polarität

Cystein Cys C Glutaminsäure Glu E Glutamin Gln Q Glycin Gly G Histidin His H Isoleucin Ile I Leucin translation Leu L Lysin Lys K Methionin Met M Phenylalanin Phe F Prolin Pro P Serin Ser S Threonin

negativ polar ungeladen polar negativ polar ungeladen polar ungeladen polar positiv polar unpolar unpolar positiv polar unpolar unpolar unpolar ungeladen polar ungeladen polar unpolar ungeladen polar

15 Bi01_29 Proteins are chains of amino acids (Polypeptides) from Brown (1999) DNA replication RNA transcription PROTEIN translation Bi01_30 Proteine sind Polypeptide Aminosäure DNA Molmasse Polarität der R-Gruppe 89,1apparatus unpolar The entropy fighting 174,4 positiv polar replication Abkürzungen* drei ein Buchstaben Buchstabe Alanin Ala A Arginin Arg R Asparagin Asn N Asparaginsäure Asp D Cystein Cys C Glutaminsäure Glu E Glutamin Gln Q Glycin Gly G Histidin His H Isoleucin Ile I Leucin translation Leu L Lysin Lys K Methionin Met M Phenylalanin Phe F Prolin Pro P Serin Ser S Threonin Thr T Tryptophan Trp W Tyrosin Tyr Y Valin Val V RNA transcription 132,1 133,1 121,2 147,1 146,2 75,1 155,2 131,2 131,2 146,2 149,2 165,2 115,1 105,1 119,1 204,2 181,2 117,2 PROTEIN ungeladen polar negativ polar ungeladen polar negativ polar ungeladen polar ungeladen polar positiv polar unpolar unpolar positiv polar unpolar unpolar unpolar ungeladen polar ungeladen polar unpolar ungeladen polar unpolar * Am häufigsten verwendet man die Standardabkürzungen mit drei Buchstaben. die Abkürzungen aus einem Buchstaben sollten nur dann benutzt werden, wenn man die Aminosäuresequenz eines Polypeptids platzsparend aufschreiben möchte. aa_table1.pdf from Brown (1999) 15

Bi01_32 energy (solar, nutri The entropy fightin replication DNA RNA

16 Living System: Closeups Bi01_31 replication transcription translation 4 letter alphabeth Genetic Code 20 letter alphabeth Living System: Closeups Bi01_32 energy (solar, nutri The entropy fightin replication DNA RNA PROTEI transcription translation Genetic Code (1994) Copyright W. Schreiner

17 Living System: Closeups Bi01_33 replication transcription translation close up of translation Translation: Overview Living System: Closeups Bi01_34 replication transcription translation 17

18 Living System: Summary Bi01_35 How does it work? Use genome information + ATP-Energy to create ordered Structures (Proteins)! substrates, nutrition (low order) 18

Basic concepts of molecular biology

Basic concepts of molecular biology Gabriella Trucco Email: gabriella.trucco@unimi.it Life The main actors in the chemistry of life are molecules called proteins nucleic acids Proteins: many different