Lecture 10 DNA Structure; Mutations

Mendel identified the patterns of inheritance without knowing about DNA

What are chromosomes made of?
What is the genetic material??
o Replication
o Storage of Information
o Expression of Information
o Variation by Mutation
Protein initially favored to be genetic material
o 20 amino acids, diversity
DNA was thought too simple
o Only 4 nucleotides
o Simple repeating polymer
Bacteria can take up exogenous DNA in several ways
o Conjugation
Receive DNA by mating with other bacteria
o Transformation
Take up DNA from the media
o Transduction
Receive DNA from bacteriophage, which are viruses of bacteria
Transformation studies with bacteria:
o Diplococcus Pneumoniae
o Infection with D. pneumoniae can kill mice
smooth strains kill mice
rough strains dont kill mice
o If you kill the bacteria with heat, the mouse doesnt die
If you kill both bacteria and then inject, the mouse dies, and theres living
smooth bacteria in the mouse
Whatever the transfer is must be the genetic material
How could you figure out what it is?
o Is it protein? DNA? RNA?
o Try using specific enzymes
Enzyme that degrade DNA: DNase
Enzyme that degrades protein: protease
Enzyme that degrades RNA: RNase
o When using DNase, the bacteria didnt come back to life, so evidence for DNA
How does DNA encode genetic information?
o Made of 4 nucleotides: A, C, G, T
o Some scientists thought all organisms had same amount of all 4
o A/T = 1.0, G/C = 1.0
Watson and Crick model for DNA structure based on 2 key pieces of data:

o Chargoffs Rules (A/T = 1, G/C = 1)

o X-Ray from Photo 51 double helix
When given a DNA strand, its 5 to 3
The Genetic Code
o Triplets of nucleotides (codons) encode protein sequence
o DNA has 4 bases: A,C,G,T
o RNA has 4 bases: A,C,G,U
o Protein has 20 amino acids
o Triplet codons code for specific amino acids
o 3 codons specify STOP: UAA, UAG, UGA
o Degenerate Code some amino acids specified by more than one triplet
What are mutations?
o Source of genetic variation
o Basis for natural selection
o Causes of diseases
o Mutation: Any change in a genes sequence (germline mutations are inherited,
somatic mutations are not)
o Wild-Type Allele: Function version of a gene found relatively frequently in
population
o Mutant Allele: Altered version of a gene with impaired/changed function relative
to wild-type
o Polymorphism: Variant of a gene that is compatible with normal (wild-type)

function
Why do mutations alter gene function?
o 1) Mutation: change in DNA sequence
o 2) Change in protein amino acid sequence
o 3) Change in protein function
o 4) Physiological effect
Types of Mutations
o Substitution (point mutation)
Just replace like A to G
o Insertion
Insert a nucleotide
Can cause a frameshift (affects protein coding frame)
o Deletion
Delete a nucleotide
Can cause frameshift (affects protein coding frame)
Types of Outcomes
o Nonsense Mutation: change one amino acid to a stop codon (aka premature stop)

o Missense Mutation: change one amino acid to another

o Silent Mutation: Nucleotide changes, but amino acid doesnt (changes to the same

amino acid)
Classifying Mutations by Consequences on Protein Function
o Loss-of-Function Mutations
Null Mutation (amorph) is a complete loss-of-function
No functional protein product
Either no product or completely non-functional product
Leaky Mutation (hypomorph) is a partial loss-of-function
Reduced function of protein product
Either less product or less functional product
What kinds of changes in DNA cause loss-of-function?
Insertion, deletion, frameshift, nonsense, missense
Null Mutation can be caused by complete deletion of gene, or early

premature stop, or point mutation in crucial amino acid

Dominant Negative Mutation
Causes protein loss-of-function, but is not recessive
Interferes with wild-type product in heterozygote, therefore
exhibits dominance
Haploinsufficient Mutation
Causes a loss-of-function of a gene that is very dosage-sensitive
One copy of gene is not enough: dominant effect of loss-of-

function in heterozygotes
o Gain-of-Function Mutations
Hypermorph Mutation
Excessive amounts of protein product
Excessive function of protein product
Typically missense mutation or deletion of regulatory region
Neomorph Mutation
New protein function is acquired
New location or timing of protein expression
Typically translocation or change in regulatory region
o Most mutations are loss-of-function