Basic Molecular Biology

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Basic Molecular Biology
Many slides by Omkar Deshpande
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Overview

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

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Human Genome Program, U.S. Department of Energy,
Genomics and Its Impact on Medicine and Society
A 2001 Primer, 2001
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(No Transcript)
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Watson and Crick
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(No Transcript)
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Macromolecule (Polymer) Monomer
DNA Deoxyribonucleotides (dNTP)
RNA Ribonucleotides (NTP)
Protein or Polypeptide Amino Acid
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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.

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Nucleotides
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DNA
A T G C
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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.

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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
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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.

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Central dogma
ZOOM IN
tRNA
transcription
DNA
rRNA
snRNA
translation
POLYPEPTIDE
mRNA
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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.

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DNA
RNA
A T G C
T ? U
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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.

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Splicing

• frgjjthissentencehjfmkcontainsjunkelm
• thissentencecontainsjunk

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Key player RNA polymerase

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

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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.

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Promoter
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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.

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3
Promoter
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Transcription key steps
DNA

• Initiation
• Elongation
• Termination

DNA

RNA
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Transcription key steps
DNA

• Initiation
• Elongation
• Termination

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Transcription key steps
DNA

• Initiation
• Elongation
• Termination

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Transcription key steps
DNA

• Initiation
• Elongation
• Termination

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Transcription key steps
DNA

• Initiation
• Elongation
• Termination

DNA

RNA
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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

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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.

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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.

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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.

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The Genetic Code
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Proteins

• Composed of a chain of amino acids.
• R
• H2N--C--COOH
• H

20 possible groups
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Proteins
R
R
H2N--C--COOH
H2N--C--COOH

H H

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Dipeptide
This is a peptide bond
R O R
II
H2N--C--C--NH--C--COOH

H H
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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.

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Our course (2427)
Part 1, DNA Assembly, Evolution, Alignment
Part 2, Genes Prediction, Regulation
Part 3, Structures Interactions
transcription
DNA
rRNA
snRNA
translation
POLYPEPTIDE
mRNA
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Computer Scientists vs Biologists(courtesy
Steven Skiena, SUNY Stony Brook)
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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.

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Computer scientists vs Biologists

• Computer scientists get high-paid jobs after
  graduation.
• Biologists typically have to complete one or more
  post-docs...

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Computer scientists vs Biologists

• Nothing is ever completely true or false in
  Biology.
• Everything is either true or false in computer
  science.