1. BIOL 350 - Principles of Genetics
• Instructors
‣ Dr.Vicki Corbin
‣ Dr. Stuart Macdonald
• Textbook
‣ Genetics: Analysis of Genes and Genomes
D. L. Hartl & E. W. Jones, 7th Edition
• Email
‣ genet350sp09@ku.edu

2. Chapter 1
Genes, Genomes & Genetic
Analysis

3. Genetics & Genomics
• Genetics
‣ The study of biologically inherited traits
‣ Includes classical transmission, molecular, population
& quantitative genetics
• Genomics
‣ The study of the sequence, organization, and
function of genomes

4. Organism → DNA

5. DNA is the Genetic Material
• Inherited traits are influenced by genes
transmitted from parents to offspring
• Genes are composed of the chemical
deoxyribonucleic acid (DNA)
• DNA is the hereditary material in all cellular
organisms

6. Griffiths (1928)
Heat-killed S Living R cells +
Living S cells Living R cells
cells heat-killed S cells
Pneumonia Healthy mouse Healthy mouse Pneumonia
Only S cells from Only R cells from R and S cells from
No cells isolated
dead mouse live mouse dead mouse
• Substance from dead S cells must be transferred to living
R cells, i.e., R bacteria can be transformed into S bacteria

7. Avery, McLeod & McCarthy (1944)
Heat-killed S
cells
Live R cells
Live S cells No live S cells
recovered recovered
• Only if DNA from S cells is destroyed will mice survive

8. Properties of DNA
1. Carries blueprint for all parts of a complex
organism - DNA must allow diversity
2. Every cell has the same genetic makeup - at every
cell division DNA must be faithfully replicated
3. Encodes all proteins made in an organism, and
signals when and where they should be made -
DNA must have informational content
4. Individuals are not genetically identical - on occasion
DNA must be able to change

9. Structure of DNA
• Watson & Crick
resolved the 3D
structure in 1953
‣ DNA consists of 2 chains
twisted into a double-
stranded helix
‣ Helix is right-handed: coils
in a clockwise direction
‣ Each strand has polarity

10. DNA Composition
• Each strand of the DNA helix is a linear
polymer of nucleotides
• Each nucleotide contains a phosphate group,
a deoxyribose sugar, and a nitrogenous base
• Four DNA bases:
Adenine (A) Thymine (T)
PURINES PYRIMIDINES
Guanine (G) Cytosine (C)

11. Complementary Base Pairing
• Base pairing rules
‣ Adenine pairs with Thymine (A − T)
‣ Cytosine pairs with Guanine (C − G)
DNA helix unwind DNA

12. DNA Replication
• Watson-Crick DNA
structure suggests a way
that DNA can be copied
‣ Strands of the original double-
stranded molecule separate
‣ Each original strand serves as
a template to create a
complementary strand (relying
on A-T and G-C base pairing)

13. Overview
Template strand
5′ 3′
3′ 5′
New strand
5′ 3′
Daughter DNA
Parent DNA molecule
molecules
3′ 5′
New strand
5′ 3′
3′ 5′
Template strand

14. Outcome of DNA Replication
• 1 double-stranded parent DNA molecule
gives 2 identical daughter copies
• Each daughter molecule has 1 parental
strand and 1 newly synthesized strand
5’ ATG CCG ATC 3’
3’ TAC GGC TAG 5’
5’ ATG CCG ATC 3’ 5’ ATG CCG ATC 3’
3’ TAC GGC TAG 5’ 3’ TAC GGC TAG 5’

15. DNA = Information
• Sequence of bases (A, C, G, & T) along a
DNA molecule encodes genetic information
‣ Huge information potential: a sequence of DNA 10
bases has 410 (> 1 million) possible forms
• A DNA molecule can encode vast number
of different proteins

16. Noncoding DNA
• Only a fraction of the total DNA in an
organism codes for protein
• What does noncoding DNA do?
‣ Regulatory DNA sequence - controls when, where,
and how much protein-coding genes are expressed
(i.e., turned on)
‣ Some DNA is transcribed into RNA molecules that
are themselves functional (and are never translated)
‣ Junk DNA - sequence with no known function

17. DNA → → Protein
• DNA sequence provides the information
encoding the amino acid sequence of a
polypeptide chain (a protein)
• BUT this is an indirect process
‣ DNA codes for RNA via transcription
‣ RNA codes for protein via translation

18. DNA → RNA → Protein
• DNA is transcribed into
the related molecule
ribonucleic acid (RNA)
• RNA transcript is
processed to form
messenger RNA (mRNA)
• mRNA translated into an
amino acid sequence (a
polypeptide) “Central Dogma”

19. Example
• Phenylalanine
hydroxylase
‣ The first 21 bases
of the gene
‣ The first 7 amino
acids in the
resulting
polypeptide

20. Transcription (DNA → RNA)
• Make an RNA molecule
complementary to a
single DNA strand
‣ Conceptually similar to DNA
replication
• RNA transcript often
processed to give the
mature mRNA
‣ Remove portions of gene not
encoding amino acids

21. RNA Transcript
• Transcription begins at an initiation site
upstream of the protein-coding region of the
gene, and ends at a termination site
downstream of the protein-coding region
transcription
PROTEIN-CODING REGION
translation

22. RNA
• RNA (ribonucleic acid) is structurally similar
to DNA
‣ RNA contains a ribose sugar (DNA contains
deoxyribose)
‣ RNA is typically single-stranded
‣ RNA contains the base Uracil (U) rather than Thymine
(T)

23. RNA-DNA Base Pairing
• In the RNA-DNA duplex formed during
transcription, U (in RNA) pairs with A (in
DNA)

24. Role of RNA Intermediate
• The mature mRNA transcript serves as a
“working copy” of the gene
• Increases number of copies of the genetic
information in the cell
‣ remember each cell hold just 2 copies of the DNA
gene
• Provides an additional level of regulation

25. Translation (RNA → Protein)
Process occurs at
ribosomes

26. Stepwise Amino Acid Addition
Polypeptide chain elongates until a “stop” codon is
found, then is released from the ribosome

27. 3 Types of RNA Used in Translation
• messenger RNA (mRNA) - carries genetic
information from the gene
• ribosomal RNA (rRNA) - major constituent
of ribosomes
• transfer RNA (tRNA) - each carries an
amino acid and an anticodon
(complementary to a mRNA codon
sequence)

28. Triplet Code
• A codon = a 3-base DNA triplet in a gene
• There are 4 (= 64) possible codons, but just
3
20 amino acids...
• Not all of the codons encode an amino acid
‣ Stop (or termination) codons
• Some amino acids are encoded by multiple
codons
‣ Triplet code is degenerate

29. The Standard Genetic Code
2nd nucleotide in codon (middle)
3rd nucleotide in codon (3′ end)
1st nucleotide in codon (5′ end)
Codon Abbreviations

30. Start & Stop Codons
• AUG (specifies Methionine) is the start
codon for polypeptide synthesis
‣ All polypeptide chains start with Met
‣ Met is also used within polypeptide chains
• UAA, UAG, UGA are the stop codons
‣ Signal end of translation and release of polypeptide
from ribosome
‣ Stop codons are not recognized by tRNA molecules

31. Universal Code?
• Triplet genetic code is almost universal, but
there are a few exceptions
• For example, the vertebrate mitochondrial
DNA genetic code:
Codon Standard Vertebrate mtDNA
AGA Arg stop
AGG Arg stop
AUA Ile Met
UGA stop Trp

32. Polypeptide → Protein
• Polypeptide resulting from
transcription/translation is
not the final protein
• Protein = folded polypeptide
chain
• Amino acid sequence helps
specify the folding - does not myoglobin
completely determine the 3D structure
protein 3D structure

33. Genes Change by Mutation
• Mutation = a heritable change in the
genome sequence
• A mutation gives a mutant gene sequence,
which will produce a mutant mRNA and
protein, and yield a mutant phenotype
‣ A phenotype is any observable quality, characteristic
or trait

34. Drosophila white Gene Mutation
• The product of the white gene operates in
the pigment synthesis pathway
• Normal, wild-type gene → red eyes
• Defective, mutant gene → white eyes
WILD-TYPE MUTANT

35. Phenylketonuria (PKU)
• Normal individual
‣ Phenylalanine (an amino acid) in
food is converted into tyrosine
by the enzyme phenylalanine
hydroxylase (PAH) Phenylalanine
• Individual with mutant hydroxylase
PAH enzyme
‣ Phenylalanine accumulates, and
excess is broken down into
harmful metabolites

36. PKU Disease
• Individuals with a PAH enzyme mutation
have mental retardation
• PKU is one of very few diseases that can be
controlled by diet (if caught early)
‣ US has tested all newborns since the 1960’s - if positive
they are put on a diet low in phenylalanine
• Incidence of PKU:
‣ 1 in 10,000 Caucasian children
‣ 1 in 200,000 African-American children

37. Wild-type PAH Enzyme
Production of
PAH enzyme in
a non-mutant
(wildtype)
individual

38. PAH: Start Codon Mutation
No PAH
enzyme is made
because
translation
cannot be
initiated

39. PAH: Mutation in Middle of Gene
Mutant form of
PAH protein is
produced that
cannot properly
metabolize
phenylalanine

40. Lots of Mutations Lead to PKU
• >100 mutations in the PAH gene result in a
malfunctioning enzyme
‣ Most are single base changes (e.g., C → T) in protein-
coding regions of the gene (exons) that lead to single
amino acid changes
‣ Some are in noncoding gene regions (introns) and
impact how the PAH mRNA is processed

41. Genes & Environment
Influence Traits
• PKU shows that a single gene can have a
major effect on a trait
• Also demonstrates that environment is very
important
‣ PKU mutations have no effect on individuals that
severly restrict their phenylalanine intake
• Many traits show this kind of gene-by-
environment interaction

42. Polygenic Traits
• PKU is unusual in that only one gene can
mutate to give the disease
• Most traits are polygenic, and are influenced
by many genes (along with environmental
factors)
‣ Most human diseases are complex traits

43. Pleiotropy
• Some genes can affect more than one trait -
gene said to have pleiotropic effects
• Example: 40% of cats with white fur and
blue eyes are also deaf
‣ The genetic factor affecting
fur and eye color can also
lead to deafness