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Class 1: Introduction
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Source: Alberts et al
The Tree of Life
The Cell
Example: Tissues in Stomach
DNA Components
Four nucleotide types:
 Adenine
 Guanine
 Cytosine
 Thymine
Hydrogen bonds:
 A-T
 C-G
Source: Alberts et al
The Double Helix
Source: Mathews & van Holde
DNA Duplication
Source: Alberts et al
DNA Organization
Genome Sizes
 E.Coli
(bacteria)
 Yeast (simple fungi)
 Smallest human chromosome
 Entire human genome
4.6 x 106 bases
15 x 106 bases
50 x 106 bases
3 x 109 bases
Genes
The DNA strings include:
 Coding regions (“genes”)
 E. coli has ~4,000 genes
 Yeast has ~6,000 genes
 C. Elegans has ~13,000 genes
 Humans have ~32,000 genes
 Control regions
 These typically are adjacent to the genes
 They determine when a gene should be
expressed
 “Junk” DNA (unknown function)
Transcription
sequences can be transcribed to RNA
Source: Mathews & van Holde
 Coding
 RNA


nucleotides:
Similar to DNA, slightly different backbone
Uracil (U) instead of Thymine (T)
RNA Editing
Source: Mathews & van Holde
RNA Editing
RNA roles
 Messenger
RNA (mRNA)
 Encodes protein sequences
 Transfer RNA (tRNA)
 Adaptor between mRNA molecules and aminoacids (protein building blocks)
 Ribosomal RNA (rRNA)
 Part of the ribosome, a machine for translating
mRNA to proteins
 ...
Transfer RNA
Anticodon:
 matches a codon (triplet of mRNA nucleotides)
Attachment site:
 matches a specific amino-acid
Translation
 Translation
is mediated by the ribosome
 Ribosome is a complex of protein & rRNA
molecules
 The ribosome attaches to the mRNA at a translation
initiation site
 Then ribosome moves along the mRNA sequence
and in the process constructs a poly-peptide
 When the ribosome encounters a stop signal, it
releases the mRNA. The construct poly-peptide is
released, and folds into a protein.
Source: Alberts et al
Translation
Source: Alberts et al
Translation
Source: Alberts et al
Translation
Source: Alberts et al
Translation
Source: Alberts et al
Translation
Genetic Code
Protein Structure
 Proteins
are polypeptides of 70-3000
amino-acids
 This
structure is
(mostly) determined
by the sequence of
amino-acids that
make up the protein
Protein Structure
Evolution
 Related
organisms have similar DNA
 Similarity in sequences of proteins
 Similarity in organization of genes along the
chromosomes
 Evolution plays a major role in biology
 Many mechanisms are shared across a wide
range of organisms
 During the course of evolution existing
components are adapted for new functions
Evolution
Evolution of new organisms is driven by
 Diversity
 Different individuals carry different variants of
the same basic blue print
 Mutations
 The DNA sequence can be changed due to
single base changes, deletion/insertion of DNA
segments, etc.
 Selection bias
Course Goals
 Computational
 We
tools in molecular biology
will cover computational tasks that are posed
by modern molecular biology
 We will discuss the biological motivation and setup
for these tasks
 We will understand the the kinds of solutions exist
and what principles justify them
Four Aspects
Biological
 What is the task?
Algorithmic
 How to perform the task at hand efficiently?
Learning
 How to adapt parameters of the task form
examples
Statistics
 How to differentiate true phenomena from
artifacts
Example: Sequence Comparison
Biological

Evolution preserves sequences, thus similar genes might
have similar function
Algorithmic

Consider all ways to “align” one sequence against
another
Learning

How do we define “similar” sequences? Use examples to
define similarity
Statistics

When we compare to ~106 sequences, what is a random
match and what is true one
Topics I
Dealing with DNA/Protein sequences:
 Genome projects and how sequences are found
 Finding similar sequences
 Models of sequences: Hidden Markov Models
 Transcription regulation
 Protein Families
 Gene finding
Topics II
Gene Expression:
 Genome-wide expression patterns
 Data organization: clustering
 Reconstructing transcription regulation
 Recognizing and classifying cancers
Topics III
Models of genetic change:
 Long term: evolutionary changes among species
 Reconstructing evolutionary trees from current day
sequences
 Short term: genetic variations in a population
 Finding genes by linkage and association
Topics IV
Protein World:
 How proteins fold - secondary & tertiary structure
 How to predict protein folds from sequences data
alone
 How to analyze proteins changes from raw
experimental measurements (MassSpec)
 2D gels
Class Structure
2
weekly meeting
 Class: Mondays 16-18
 Targil: Tuesday 18-20
Grade:
 60% in five question sets
 Each contains theoretical problems & practical
computer questions
 40% test
 5% bonus for active participation
Exercises & Handouts
 Check
regularly
http://www.cs.huji.ac.il/~cbio