Basic Molecular Biology

Many slides by Omkar Deshpande

Overview

Structures of biomolecules Central Dogma of Molecular Biology Overview of this course Computer scientists vs Biologists

Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Medicine and Society: A 2001 Primer, 2001

Watson and Crick

Macromolecule (Polymer)

Monomer

DNA Deoxyribonucleotides (dNTP)

RNA Ribonucleotides (NTP)

Protein or Polypeptide Amino Acid

Nucleic acids (DNA and RNA)

Form the genetic material of all living organisms.

Found mainly in the nucleus of a cell (hence “nucleic”)

Contain phosphoric acid as a component (hence “acid”)

They are made up of nucleotides.

Nucleotides

Phosphate Group

Sugar

NitrogenousBase

Phosphate Group

Sugar

NitrogenousBase

T

C

A

C

T

G

G

C

G

A

G

T

C

A

G

C

DNA

A = T

G = C

The gene and the genome

Genome = The entire DNA sequence within the nucleus.

The information in the genome is used for protein synthesis

A gene is a length of DNA that codes for a (single) protein.

How big are genomes?

Organism Genome Size (Bases) Estimated Genes

Human (Homo sapiens) 3 billion 30,000

Laboratory mouse (M. musculus)

2.6 billion 30,000

Mustard weed (A. thaliana) 100 million 25,000

Roundworm (C. elegans) 97 million 19,000

Fruit fly (D. melanogaster) 137 million 13,000

Yeast (S. cerevisiae) 12.1 million 6,000

Bacterium (E. coli) 4.6 million 3,200

Human immunodeficiency virus (HIV)

9700 9

Repeats

The DNA is full of repetitive elements (those that occur over & over & over)

There are several type of repeats, including SINEs & LINEs (Short & Long Interspersed Elements) (1 million just ALUs) and low complexity elements.

Their function is poorly understood, but they make problems more difficult.

Central dogma

DNA

tRNA

rRNA

snRNA

mRNA

transcription

translation

POLYPEPTIDE

ZOOM IN

Transcription

The DNA is contained in the nucleus of the cell.

A stretch of it unwinds there, and its message (or sequence) is copied onto a molecule of mRNA.

The mRNA then exits from the cell nucleus.

T

C

A

C

T

G

G

C

G

A

G

T

C

A

G

C

G

A

G

U

C

A

G

C

DNA RNA

A = T

G = C

T U

More complexity

The RNA message is sometimes “edited”. Exons are nucleotide segments whose

codons will be expressed. Introns are intervening segments (genetic

gibberish) that are snipped out. Exons are spliced together to form mRNA.

Splicing

frgjjthissentencehjfmkcontainsjunkelm

thissentencecontainsjunk

Key player: RNA polymerase

It is the enzyme that brings about transcription by going down the line, pairing mRNA nucleotides with their DNA counterparts.

Promoters

Promoters are sequences in the DNA just upstream of transcripts that define the sites of initiation.

The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated.

5’Promoter 3’

Promoters

Promoters are sequences in the DNA just upstream of transcripts that define the sites of initiation.

The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated.

5’Promoter 3’

Transcription – key steps

Initiation

Elongation

Termination

+

DNA

RNA

DNA

Transcription – key steps

Initiation

Elongation

Termination

DNA

Transcription – key steps

Initiation

Elongation

Termination

DNA

Transcription – key steps

Initiation

Elongation

Termination

DNA

Transcription – key steps

Initiation

Elongation

Termination

+

DNA

RNA

DNA

Genes can be switched on/off

In an adult multicellular organism, there is a wide variety of cell types seen in the adult. eg, muscle, nerve and blood cells.

The different cell types contain the same DNA though.

This differentiation arises because different cell types express different genes.

Promoters are one type of gene regulators

Transcription (recap)

The DNA is contained in the nucleus of the cell.

A stretch of it unwinds there, and its message (or sequence) is copied onto a molecule of mRNA.

The mRNA then exits from the cell nucleus. Its destination is a molecular workbench in

the cytoplasm, a structure called a ribosome.

Translation

How do I interpret the information carried by mRNA to the Ribosome?

Think of the sequence as a sequence of “triplets”.

Think of AUGCCGGGAGUAUAG as AUG-CCG-GGA-GUA-UAG.

Each triplet (codon) maps to an amino acid.

The Genetic Code

f : codon amino acid 1968 Nobel Prize in medicine – Nirenberg

and Khorana Important – The genetic code is universal! It is also redundant / degenerate.

The Genetic Code

Composed of a chain of amino acids.

R

|

H2N--C--COOH

|

H

Proteins

20 possible groups

R R | | H2N--C--COOH H2N--C--COOH | | H H

Proteins

Dipeptide

R O R | II | H2N--C--C--NH--C--COOH | | H H

This is a peptide bond

Protein structure

Linear sequence of amino acids folds to form a complex 3-D structure.

The structure of a protein is intimately connected to its function.

The 3-D shape of proteins gives them their working

ability – the ability to bind with other molecules.

Our course (2427)

DNA rRNA

snRNA

mRNA

transcription

translation

POLYPEPTIDE

Part 1, DNA: Assembly, Evolution, Alignment

Part 2, Genes: Prediction, Regulation

Part 3, Structures & Interactions

Computer Scientists vs Biologists

(courtesy Steven Skiena, SUNY Stony Brook)

Computer scientists vs Biologists

Biologists strive to understand the very complicated, very messy natural world.

Computer scientists seek to build their own clean and organized virtual worlds.

Computer scientists vs Biologists

Computer scientists get high-paid jobs after graduation.

Biologists typically have to complete one or more post-docs...

Computer scientists vs Biologists

Nothing is ever completely true or false in Biology.

Everything is either true or false in computer science.