introduction to molecular and cell biology

7/27/2019 Introduction to Molecular and Cell Biology

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Ulf Schmitz, Introduction to molecular and cell biology 1

www. .uni-rostock.de

BioinformaticsBioinformaticsIntroduction to molecular and cell biologyIntroduction to molecular and cell biology

Ulf [email protected]

Bioinformatics and Systems Biology Groupwww.sbi.informatik.uni-rostock.de


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Outline

1. Recommended Literature

2. What is Bioinformatics?3. The Cell

4. Molecular Biology / Genomics

1. Genes

2. DNA

3. RNA4. Proteins

5. Gene Expression

5. Signaling Pathways

6. Outlook next lecture


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Recommended Literature

Developing Bioinformatics Computer Skil ls; CynthiaGibas & Per Jambeck; OReilly; ISBN: 1565926641

New Biology for Engineers and Computer Scientists;Aydin Tzeren & Stephen W.Byers; Pearson Prentince HallBioengineering; ISBN: 0130664634

Bioinformatics: Sequence and Genome Analysis; DavidW. Mount; Cold Spring Harbor; ISBN: 0879697121

Introduction To Bioinformatics; Arthur M. Lesk; OxfordUniversity Press ISBN: 0199277877


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What is Bioinformatics?

Bioinformatics: is the development and use of computer

applications for theAnalysis, Interpretation, Simulation andPrediction of biological Systems and corresponding

experimental methods in nature sciences.


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Chemistry

Mathematics

Statistics

Computer Science

Informatics

Physics

Medicine

Biology

Molecular Biology

Bioinformatics

What is Bioinformatics?


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History of Bioinformatics

Biologists were searching for algorithms to analyze andinterpret their huge amount of empiric biological data

As well as computer aided modeling and simulation

International molecular biological databases arose to

make data internationally accessible and comparable

Algorithms for gene- and protein prediction wheredeveloped

These efforts lead to the development of artificialneuronal networks, genetic algorithms and evolutionstrategies


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Bioinformatics

Offers an ever more essential input to

Molecular Biology Pharmacology (drug design)

Agriculture

Biotechnology Clinical medicine

Anthropology

Forensic science

Chemical industries (detergent industries, etc.)


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Organism, Organ, Cell

Organism

Organ


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The ER modifies proteins, makes macromolecules,

and transfers substances throughout the cell.

Ribosome translates

mRNA into a polypeptidechain (e.g., a protein).

Mitochondrion

manufactures adenosine

triphosphate (ATP), which

is used as a source of

energy.

The Cell

circa 100 trillion (1014) cells in a human organism

200 different forms of cells

Nucleus only in

eukaryotic cells.

Contains most of the

cell's genetic material.


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Molecular Biology

... is the study of biology at a molecular level.

The field overlaps with other areas of biology, particularly genetics andbiochemistry

Molecular biology concerns itself with understanding the interactions

between the various systems of a cell, including the interrelationship ofDNA, RNA and protein synthesis and learning how these interactions areregulated.

Schematic relationship between biochemistry, genetics and molecular biology

Function

GenesProteins

Biochemistry

Molecular Biology

Genetics


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Biochemistry and Genetics

Biochemistry is the study of molecules (e.g.proteins). Biochemists take an organism or cell anddissect it into its molecular components, such asenzymes, lipids and DNA, and reconstitute them intest tubes (in vitro).

Genetics is the study of the effect of geneticdifferences on organisms. Often this can beinferred by the absence of a normal component

(e.g. one gene).


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From Genes to Proteins

DNA

mRNA

Protein

Gen


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The Human Genome -- 26 June 2000


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DNA

~6 billion base pairs

in every cell build the

human genome

genes form only 1,5% of

the human genome

a gene is a segment ofthe DNA, that encodes

the constructon plan for a

protein

in humans there are ca.30,000 genes only


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Chromosome

81,691,216157617

89,995,999109816

100,114,055112215

105,311,216109814

114,151,65674813

133,464,434165212

134,978,784209311

135,480,874144010

134,505,81912999

145,908,73811278

158,431,29914437

170,740,54119636

180,967,29516435

191,610,52312974

199,411,73120323

243,315,02822882

245,203,89829681

BasesGenesChrom.

A chromosome is a very long, continuous piece of DNA, which contains many

genes, regulatory elements and other intervening nucleotide sequences.

50,961,097231Y

152,634,1661184X

49,476,97228822

46,976,53730321

63,644,86892720

63,790,860145419

77,753,51076618

BasesGenesChrom.

http://www.tqnyc.org/NYC040844/Mitosis.htm


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Chromosome

Karyogram of human female

~1200Fern (Farn)

42Wheat

~380Butterflies

40Pig

104Carp (Karpfen)

32Earthworm

78Chicken

24edible snail

64Horse16Dove (Taube)

54Sheep

16Guinea Pig

48Ape

14Rye (Roggen)

46Human

8Fruit Fly

# of chromosomesSpecies

http://www.answers.com/topic/human-karyogram-png


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DNA - Sequence

. . . . . acct c ct gt gcaaga acat gaaaca cct gt ggt t c t t cct t ct cc

t ggt ggcagc t cccagat gg gt cct gt ccc aggt gcacct gcaggagt cg

ggcccaggac t ggggaagcc t ccagagct c aaaaccccac t t ggt gacac

aact cacaca t gcccacggt gcccagagcc caaat ct t gt gacacacct c

ccccgt gccc acggt gccca gagcccaaat ct t gt gacac acct ccccca

t gcccacggt gcccagagcc caaat ct t gt gacacacct c ccccgt gccc

ccggt gccca gcacct gaac t ct t gggagg accgt cagt c t t cct ct t cc

ccccaaaacc caaggat acc ct t at gat t t cccggacccc t gaggt cacg

t gcgt ggt gg t ggacgt gag ccacgaagac cccgaggt cc agt t caagt ggt acgt ggac ggcgt ggagg t gcat aat gc caagacaaag ct gcgggagg

agcagt acaa cagcacgt t c cgt gt ggt ca gcgt cct cac cgt cct gcac

caggact ggc t gaacggcaa ggagt acaag t gcaaggt ct ccaacaaagc

aaccaagt ca gcct gacct g cct ggt caaa ggct t ct acc ccagcgacatcgccgt ggag t gggagagca at gggcagcc ggagaacaac t acaacacca

cgcct cccat gct ggact cc gacggct cct t ct t cct ct a cagcaagct c

accgt ggaca agagcaggt g gcagcagggg aacat ct t ct cat gct ccgt

gat gcat gag gct ct gcaca accgct acac gcagaagagc ct ct c. . . . .


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DNA - Deoxyribonucleic acid

Deoxyribonucleic acid (DNA) forms adouble stranded helix.

A sugar-phosphate backbone forms the

outer shell on the helix

The two strands of DNA run in oppositedirections.

Bases face towards each other and formhydrogen bonds

carries the generic instructions (genes)

Nucleic acids

Cytosine - C

Guanine - G

Adenine - A

Thymine - T

complementary base pairs


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A nucleotide is an organic molecule build of three components:

one out of five bases (A, G, C, T and U in RNA), a pentose sugar

(deoxyribose in DNA or ribose in RNA) and a phosphate group.

Nucleoside = Nucleobase + Pentose

Nucleotide = Nucleobase + Pentose + Phosphate Group

Thymidin monophosphate (TMP)ThymidinThymine (T)

Cytidine monophosphate (CMP)CytidinCytosine (C)

Guanosine monophosphate (GMPGuanosinGuanine (G)

Adenosine monophosphate (AMP)AdenosineAdenine (A)

nucleotidenucleosidefree base


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GMP

HO

OH

O

P O

HO

ONH2N

N

N NH

NH2

CMP

HO

OH

O

P O

HO

O

NH2

N N

O

TMP

HO

OH

O

P O

HO

O

O

N NH

CH3

O

HO

OH

O

P O

HO

ONH2N

N

N N

AMP

PhosphateSugar

Base

12

54

3

1

2

54

3


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DNA

C G C T

S S S S

P P P P P

P P P P P

S S S S

C G C T

G C G A

S S S S

P P P P PSugar Phosphate Backbone

Base pairhydrogen bond

base

sugar

phosphate

5

3

3

5

[read as 3 prime and 5 prime]

A

T

A

T

C

G

T

A

C

G

C

G

T

A

G

C

A

T

G

C

T

C

A

T

T

A

C

G

C

G

A

T

G

C

G

C

T

A


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DNA - Molecule

CCTAGACATTGCTTTCCCATCCTGCTACTCAATGACAGTTTCTGGTTTCACTGGGTCACTCTCATCTTGATGCACTCCCGGGCAAGAGCTAACTGAAAGGCAGCTGCGTAACACATACCA GACACAACAGTTTATCATGGGAGAGTGAATTAAACCAGGAA...

DNA-sequence (Alphabet: ATGC)


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RNA Ribonucleic acid

In RNA the base Thymine (T) is replaced by Uracil (U). The other difference

to DNA is that the sugar (Pentose) will be Ribose instead of Deoxiribose.

Ribose has an additional hydroxyl group.

Bases:

Cytosine - C

Guanine - G

Adenine - A

Uracil - U

Uracil

RNA transmits genetic information from DNA (via transcription) into

proteins (by translation).

RNA is almost exclusively found in the single-stranded form.


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RNA Ribonucleic acid

RNA plays several roles in biology:

Messenger RNA (mRNA) is transcribed directly from a gene's DNA and is used to

encode proteins.

RNA genes are genes that encode functional RNA molecules; in contrast to mRNA,

these RNA do not code for proteins. The best-known examples of RNA genes are

transfer RNA (tRNA) and ribosomal RNA (rRNA). Both forms participate in the

process of translation, but many others exist.

RNA forms the genetic material (genomes) of some kinds of viruses.

Double-stranded RNA (dsRNA) is used as the genetic material of some RNA viruses

and is involved in some cellular processes, such as RNA interference.


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Proteins

Proteins have a variety of roles that they must fulfil:

1. they are the enzymes that rearrange chemical bonds.

2. they carry signals to and from the outside of the cell,and within the cell.

3. they transport small molecules.4. they form many of the cellular structures.

5. they regulate cell processes, turning them on and off

and controlling their rates.


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Proteins Amino Acids

there are 20 different types of amino acids (see below).

different sequences of amino acids fold into different 3-D

shapes.

Proteins can range from fewer than 20 to more than 5000

amino acids in length.

Each protein that an organism can produce is encoded in

a piece of the DNA called a gene.

the single-celled bacterium E.coli has about 4300

different genes.

Humans are believed to have about 30,000 different

genes (the exact number as yet unresolved),


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Protein-Sequence(Alphabet:ACDEFGHIKLMNPQRSTVWY):

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLK...

a typical human cell

contains about 100 million

proteins of about 10,000

types

CAT,CACHHistidine

TAA,TAG,TGA*Terminator (Stop)

CCT,CCC,CCA,CCGPProline

TGGWTryptophan

TAT,TACYTyrosine

TTT,TTCFPhenylalanine

CAA,CAGQGlutamine

AAT,AACNAsparagine

CGT,CGC,CGA,CGG,AGA,AGGRArginine

AAA,AAGKLysine

GAT,GAC,AAT,AACDAspartic Acid

GAA,GAGEGlutamic Acid

ATGMMethionine

TGT,TGCCCysteine

ACT,ACC,ACA,ACGTThreonine

TCT,TCC,TCA,TCG,AGT,AGCSSerine

ATT,ATC,ATAIIsoleucine

TTG,TTA,CTT,CTC,CTA,CTGLLeucine

GTT,GTC,GTA,GTGVValine

GCT,GCC,GCA,GCGAAlanine

GGT,GGC,GGA,GGGGGlycine

Triplet1-letter codeName


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Properties of amino acids:

play a role in the construction of 3-D stuctures in proteins


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Proteins

Primary protein structure

is the sequence of a chain of amino acids

Secondary protein structure

occurs when the sequence of

amino acids are linked by hydrogen

bonds.

Tertiary protein st ructureoccurs when certain attractions

are present between alpha helices

and pleated sheets.

Quaternary protein st ructureis a protein consisting of more

than one amino acid chain.


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Proteins


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Proteins - Summary

DNA sequence determines protein

sequence Protein sequence determines protein

structure

Protein structure determines protein folding

and function


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Gene Expression


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Transcription

i k d


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Gene Expression - Transcription

Messenger RNA (mRNA)

Messenger RNA is RNA that carries information from DNA to the ribosome sites ofprotein synthesis in the cell.

Once mRNA has been transcribed from DNA, it is exported from the nucleus into the

cytoplasm, where it is bound to ribosomes and translated into protein.

Non-coding RNA or "RNA genes"

RNA genes (sometimes referred to as non-coding RNA or small RNA) are genes that

encode RNA that is not translated into a protein. The most prominent examples of RNA

genes are transfer RNA (tRNA) and ribosomal RNA (rRNA), both of which are involved in

the process of translation.

i t k d


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Translation

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Translation

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Translation

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Gene Expression - Translation

The genetic code is made up ofthree letter 'words' (termed a

codon) formed from a sequence of

three nucleotides (e.g.. ACT, CAG,

TTT).

These codons can then be

translated with messenger RNA

and then transfer

RNA, with a codon correspondingto a particular amino acid.

Since there are 64 possible

codons, most amino acids have

more than one possible codon.

There are also three 'stop' or

'nonsense' codons signifying the

end of the coding region.

CAT,CACHHistidine

TAA,TAG,TGA*Terminator

CCT,CCC,CCA,CCGPProline

TGGWTryptophan

TAT,TACYTyrosine

TTT,TTCFPhenylalanine

CAA,CAGQGlutamine

AAT,AACNAsparagine

CGT,CGC,CGA,CGG,AGA,AGGRArginine

AAA,AAGKLysine

GAT,GAC,AAT,AACDAspartic Acid

GAA,GAGEGlutamic Acid

ATGMMethionine

TGT,TGCCCysteine

ACT,ACC,ACA,ACGTThreonine

TCT,TCC,TCA,TCG,AGT,AGCSSerine

ATT,ATC,ATAIIsoleucine

TTG,TTA,CTT,CTC,CTA,CTGLLeucine

GTT,GTC,GTA,GTGVValine

GCT,GCC,GCA,GCGAAlanine

GGT,GGC,GGA,GGGGGlycine

Triplet1-Letter NicknameName

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A gene codes for a protein

CCTGAGCCAACTATTGATGAA

PEPTIDE

CCUGAGCCAACUAUUGAUGAA

www. .uni-rostock.deMetabolic networks


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next level of the functional/organisational hierarchy

Protein networks guide the biochemistry of living cellsProtein networks guide the biochemistry of living cells

Kegg database

(Japan)

www. .uni-rostock.deLevels of the functional/organizational


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Levels of the functional/organizational

hierarchy


O l k i l


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Outlook coming lecture

Genomics

Proteomics



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Introduction to molecular and cell biologyIntroduction to molecular and cell biology

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