Introduction to Molecular

Biology

EECS 458

Jing Li, Ph.D.

EECS, CWRU
 Readings
• A primer on molecular biology
• Biology in a nutshell (both are on Canvas)
• Molecular Biology of the Cell by Alberts et al. Ch1-8
http://www.ncbi.nlm.nih.gov/books/NBK21054/
• Molecular Cell Biology by Lodish et al Ch1-4
http://www.ncbi.nlm.nih.gov/books/NBK21475/
• Molecular Biology by Weaver, Ch 1-3 available at
case.edu/coursesmart
• http://learn.genetics.utah.edu
 Roadmap
• Cell
• DNA
• RNA
• Protein
• Central dogma
• Genetic code
• Gene structure
• Human Genome
• Genetic variation
• Online databases
• Model organisms
The Cell

Lodish et
 Cell Structure:
Prokaryotes and Eukaryotes
• Prokaryotes:
– Single cells without nucleus, (generally)
no internal membranes, like bacteria

• Eukaryotes:
– Multicellular- nucleus, genetic materials
in nucleus, all higher organisms
Youtube video:
https://www.youtube.com/watch?v=URUJD5NEXC8
 DNA
• Deoxyribonucleic acid
• Double stranded chain of nucleotides.
• A nucleotide is a single chemical unit
with common structure: a phosphate
group linked to a five-carbon sugar
molecule as the backbone and one of
the four bases (A,T,G,C).
• The five carbons in a sugar molecule
are labeled 1’ through 5’
• https://www.youtube.com/watch?v=qy8dk5iS1f0
• https://www.youtube.com/watch?v=o_-6JXLYS-k
Nucleotide Bases
Watson-Crick
 DNA Replication
• The process of DNA to make an exact copy of
itself.
• Denaturation: strand separation (by raising
temperature).
• Renaturation: two separated complementary
strands to reform a double helix.
• Hybridization: two separated strands to
reform a double helix (the extend of
hybridization depends on their
complementary).
• https://www.youtube.com/watch?v=dKubyIRiN84
 RNA
• Ribonucleic acid
• Single stranded
• U (Uracil) instead of T (Thymine)
• Less stable than DNA
• Multiple types:
– mRNA (messenger)
– tRNA (transfer)
– rRNA (ribosomal)
https://www.youtube.com/watch?v=0Elo-zX1k8M
 Protein
• A protein is a chain of amino acids.
• Each amino acid has a central carbon (Ca),
an amino (NH2) group, a carboxyl (COOH)
group, a hydrogen (H) atom, and one side
chain (R)
• 20 amino acids vary only at side chains (R)
20 amino acids:
Alanine(A), Cysteine(C),
Aspartic Acid(D),
Glutamic Acid(E),
Phenylanine(F), Glycine(G),
Histidine (H), Isoleucine (I),
Lysine (K), Leucine(L),
Methionine(M),
Asparagine(N),
Proline(P),Glutamine (Q),
Arginine (R), Serine(S),
Threonine (T), Valine (V),
Tryptophan(W),Tyrosine(Y)
 Amino acids are linked by
peptide bonds between the
carboxyl and amino group.

Proteins consist of 100-5000aa.

Typical length: 300aa.
 Protein Structure & Function
• Primary structure: linear order of aa
from N-terminus to C-terminus
• Secondary structure: α-helices, β-
sheets
• Tertiary structure: the 3D conformation
• Quaternary structure: protein-protein
interactions.
• https://www.youtube.com/watch?v=qBRFIMcxZNM

Key: function is derived from 3D structure, and

3D structure is specified by amino acid sequence.
 Protein functions
• Metabolism
• Energy
• Transcription, protein synthesis, and
protein processing.
• Transport and motor proteins
• Communication (intra- or intercellular).
• Cell cycle.
 Central Dogma
Replication

DNA Transcription

Reverse Transcription

RNA Translation

Protein
https://www.youtube.com/watch?v=WsofH466lqk
 Genes
• A gene is a segment of nucleic acid
sequence that is necessary for the
synthesis of a functional polypeptide/
protein.
• It includes preceding and following the
coding region (UTR) and “introns”
• Only a small part of genome contains
genes. “Junk DNA”
• Genes lie in non-repetitive DNA region.
 Gene expression level
• Current abundance of mRNA (or the
rate of synthesis of mRNA)
• Regulation: transcription factors (TFs),
bind to TF binding sites in the gene
promoters in the DNA, to start
transcription.
 Translation
• The process to make a protein from
mRNA.
• Take place inside ribosomes, which are
made of rRNA and proteins.
• tRNA will bring amino acids in.

• https://www.youtube.com/watch?v=gG7uCskUOrA
• https://www.youtube.com/watch?v=fOl7lrNuOnk
 Genetic Code
• There are 4 bases (A,C,G,T) in DNA
and 4 (A,C,G,U) in RNA, but there are
20 amino acids. How amino acids are
encoded in mRNA? 41=4, 42=16, 43=64
• The actual genetic code used by cells is
a triplet code. Each triplet is called a
codon. Start codon: AUG. Stop codons:
UAA, UGA, and UAG.
Genetic Code
 Open Reading Frame
Reading frame:

Open reading frame: starts with the start

codon (AUG), and continue in triplets to
a termination codon. It’s important in
gene prediction.
 Expression of Proteins
• Translation
• (Posttranslational) modification (not for
all proteins)
• Translocation (not for all proteins)
• Degradation
 Genome

• The entire DNA sequences in an

organism.
• In higher organisms, DNA is contained in
chromosomes.
• The number of chromosomes is a
character of a specie. Chromosomes
appear in pairs in most higher organisms.
(human 23 pairs).
Human Chromosomes
22 pairs of autosomes, 1
pair sex chromosomes.
The DNA/genes on a pair of
chromosomes are not
the same. (Alleles)
The two alleles at one
position is called a
genotype.
The alleles on one
chromosome is called a
haplotype.
Exactly one chromosome
from a pair will occur in a
sperm/egg.
 Human Genome
• Contains 3 billion bases.
• The total number of genes is estimated
around 25,000.
• Less than 2% DNAs code proteins.
• Repeats make up half of the genome.
• The size of a gene is on average 3,000
bases, but vary greatly.
• More than half of predicted genes are
function-unknown.
 Human Genome
• Genes appear to be clustered randomly
along the genome. Gene dense regions
are predominantly G/C rich regions.
• CpG islands form barriers between
genes and “junk DNA”
• 99.9% nucleotides are the same in all
humans.
• Single nucleotide differences (SNPs)
occur every 500-1k bases.
Cell Division

https://www.youtube.com/watch?v=C6hn3sA0ip0
https://www.youtube.com/watch?v=Q6ucKWIIFmg
 Cell Division

https://www.youtube.com/watch?v=nMEyeKQClqI
 Beyond the cell
• Cell Communication
• Evolution
– Genotype, phenotype
– Selection: phenotypic changes may lead to
differential reproductive success
– Mutations
– Speciation
– Homolog (similarity), ortholog (different
species), paralog (within a genome)
 Genetic diversity
• Mutations:
– point mutation/substitution, single
nucleotide polymorphisms (SNPs)
– Insertion
– Deletion
– Inversion (rearrangement)
– Translocation (rearrangement)
– Duplication
– Detrimental, beneficial, neutral
• Sexual reproduction
Molecular Biology Data
Molecular Biology Data
Databases: sequences
Databases: expression
Databases: protein
Databases: others
 Model organisms
• E. coli (bacterium)
• Yeasts (S. cerevisiae)
• C elegan (worm)
• Arabidopsis (plant)
• Drosophila (fruit fly)
• Zebrafish
• Mouse
 Challenges: Genome Structure
Analysis

• Genome comparison
• Gene finding
• Understanding transcriptional regulation
 Challenges: phenotype 
genotype

• Population genetics
• Diagnosis
• Therapy optimization
• Target finding
• Systems biology
 Challenges: Protein Property
Prediction

• Structure prediction
• Function prediction
• Genetic network reconstruction
• Docking
 Image Credits
• U.S. Department of Energy Human
Genome Program, http://www.ornl.gov/hgmis
• Molecular Cell Biology. 4th ed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books
• Access Excellence, Graphics Gallery
http://www.accessexcellence.org/AB/GG/

Some materials from “A

primer on molecular
biology” by Alexander Zien