BIO513: Lecture 1. Central dogma “The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information.

BIO513: Lecture 1

Central dogma

“The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid.”

-Francis Crick

The Alphabet of DNA

• DNA consists of a 4 letter alphabet, arranged in complementary pairs on a sugar/phosphate backbone– A (adenine, a purine) – C (cytosine, a pyrimidine)– G (guanine, a purine)– T (thymine, a pyrimidine)

Bonds

• There are strict rules for the complementary strands (with nucleotides linked by a hydrogen bond).

A – T

C – G

G – C

T – A

DNA double helix

http://academic.brooklyn.cuny.edu

Gene and Genomics

• A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring.

• The genome of an organism is its hereditary information encoded in DNA

Species Genome size (Mb) Number of genes  

Mycoplasma genitalium 0.58 500

Streptococcus pneumoniae 2.2 2300

Escherichia coli 4.6 4400

Saccharomyces cerevisiae 12 5800

Arabidopsis thaliana 125 25,500

Caenorhabditis elegans 97 19,000

Sea urchin 814 23,300

Drosophila melanogaster 180 13,700

Mus musculus 2500 ~21,000

Homo sapiens 2900 20-25,000

Oryza sativa 466 45-55,000  

RNA

• RNA is very similar to DNA

• RNA is usually single-stranded, while DNA is usually double-stranded

• RNA nucleotides contain ribose while DNA contains deoxyribose.

• and RNA has the base uracil rather than thymine that is present in DNA.

RNA structure

Transcription: from DNA to RNA

• A

• C

• G

• T

DNA RNA

• U

• G

• C

• A

TATA

activator

TFIID

Steps of gene transcription

Pol II Pol II

TATA

Steps of gene transcription

activator

TFIID

Pol II Pol II

TATA

Steps of gene transcription

Pol II Pol II

Transcription factors recognizes specific sequences

AGCTGGT gene 1AGCTGGT gene 2AGCTGGT gene 3CGCTGGT gene 4CGCTGGT gene 5CGCTGGT gene 6GGCTGGT gene 7GGCTGGT gene 8GGCTGGT gene 9TGCTGGT gene 10TGCTGGT gene 11TGCTGGT gene 12.... ...

Motif logo

Protein

• Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds.

• Proteins are used to execute almost all cell functions (signaling, enzyme, structure, regulation, etc.)

• The biological functions of a protein is defined by its structure and ability to bind.

Translation

• mRNA is used as the template for protein synthesis.

• Proteins are made in the cytoplasm (outside of the nucleus).

• Translation starts from the AUG (START) codon.

U C A G

U Phe Ser Tyr Cys U

Phe Ser Tyr Cys C

Leu Ser STOP STOP A

Leu Ser STOP Trp G

C Leu Pro His Arg U

Leu Pro His Arg C

Leu Pro Gln Arg A

Leu Pro Gln Arg G

A Ile Thr Asn Ser U

Ile Thr Asn Ser C

Ile Thr Lys Arg A

Met Thr Lys Arg G

G Val Ala Asp Gly U

Val Ala Asp Gly C

Val Ala Glu Gly A

Val Ala Glu Gly G

Genetic Code:

Three nucleotides (CODON) determine a amino acid.

64 possible codons correspond to 20 amino acids.

Example:AAA, AAG - Lysine

Topics of reading

1. Genome sequencing technologies and their impact on public health approaches

2. Analysis of gene expression

3. Transcription factor regulation and motif finding

4. Epigenetics and its role in transcription regulation, development, and diseases.

5. Network structure analysis

6. Tools and paradigms for network analysis

7. Role of networks in offering systems level insights in interpretation of disease

8. Genetic variation within human population

9. Genome diversity in microbial pathogens 

Genome sequencing technologies and their impact on public health approaches

• What is “next-generation” sequencing?• How do you search for a short DNA sequence fragment

in a genome or large database?

Genome sequencing technologies and their impact on public health approaches

• What is “next-generation” sequencing?• How do you search for a short DNA sequence fragment

in a genome or large database?

Mardis 2008

Genome sequencing technologies and their impact on public health approaches

• What is “next-generation” sequencing?• How do you search for a short DNA sequence fragment

in a genome or large database?

Mardis 2008

Trapnell et al. 2009

Analysis of gene expression• Which genes are expressed in a given cell type under a

specific environmental condition?

• What do these expressed genes do?

• What genes are expressed differently between disease and normal tissues?

Analysis of gene expression

Hughes et al. 2000

• Which genes are expressed in a given cell type under a specific environmental condition?

• What do these expressed genes do?

• What genes are expressed differently between disease and normal tissues?

Transcription factor regulation and motif finding

• How are gene expression levels regulated?• To what extent is the gene expression pattern encoded

in the genome?

Transcription factor regulation and motif finding

• How are gene expression levels regulated?• To what extent is the gene expression pattern encoded

in the genome?

Epigenetics and its role in transcription regulation

• Why are different sets of genes expressed in different cell-types?

• How is tissue-specific regulatory information inherited?

Epigenetics and its role in transcription regulation

• Why are different sets of genes expressed in different cell-types?

• How is tissue-specific regulatory information inherited?

Mikkelsen 2007

Tools and paradigms for network analysis

• How do the all the genes/proteins inside a cell interact with each other?• How can we reconstruct a biological network from experimental data?

Tools and paradigms for network analysis

• How do the all the genes/proteins inside a cell interact with each other?• How can we reconstruct a biological network from experimental data?

Friedman 2004

Network structure analysis

• Is a biological network made of modules?

• How does a biological network differ from a random network?

• Does biological networks change during development and evolution?

Network structure analysis

• Is a biological network made of modules?

• How does a biological network differ from a random network?

• Does biological networks change during development and evolution?

Milo et al. 2002Kim et al. 2008

Network interpretation of diseases• What does network analysis tell us about diseases?

Network interpretation of diseases• What does network analysis tell us about diseases?

Segal et al. 2004

Genetic variation within human population• How similar are the genome sequences of two random

individuals?• How much variation of gene expression can be linked to

genetic differences?

Genetic variation within human population• How similar are the genome sequences of two random

individuals?• How much variation of gene expression can be linked to

genetic differences?

Altschuler et al. 2008

Genome diversity in microbial pathogens

• How many microorganisms are there living inside a human being?

• How do these microorganisms contribute to normal physiology and diseases?

Genome diversity in microbial pathogens

• How many microorganisms are there living inside a human being?

• How do these microorganisms contribute to normal physiology and diseases?

Turnbaugh et al. 2007