DNA mutation and repair

Mutation

Any change made to the DNA sequence or chromosome structure

Can lead to disease/death, but can also create ________ (evolution)

new alleles

Example of mutations:

HbS , malaria, sickle-cell anemia

Mutations are

permanent – can’t be removed or repaired

They do not selectively occur (____)

random

Do Abics cause Abicr mutations?

No

Mutations are classified in different ways

Size, cause, type of cell that contains mutated DNA, and 
other classes of mutations

Size

Mutations can either involve large portions of chromosomes or small regions

Chromosomal mutations

Large segments of chromosomes are deleted,

inverted, moved, or duplicated

Gene mutations

Smaller changes in the DNA sequence

What causes mutations

Spontaneous mutations and induced mutations

Spontaneous mutations

Some due to natural biochemical events

Induced mutations

Others helped along by some artificial factor (chemicals, radiation, viral)

Type of cell that contains mutated DNA

Somatic mutations = Arise in the DNA of somatic cells (normal diploid)

Somatic cells _____ passed onto the next generation

never

Germ-line mutations = Mutations arise in the DNA of

gamete-forming

Transmitted to the offspring

Pass onto future generations

Other classes of mutations

Some are incompatible with life (lethal mutations)

Conditional mutations

Some only produce an effect under certain environmental conditions

such as hot temperatures

Suppressor mutations

Some reverse (suppress) the effect of a previous

mutation 

Intragenic

2nd mutation in the same gene

- Mutation 1 alters protein structure, 2 alters it back

Small gene mutations come in 3 main varieties:

Base-pair substitutions, insertions/deletions, and expansion of trinucleotide repeats (TNRE)

Possible outcomes on the amino acid sequence

Silent mutation, missense mutation, and nonsense mutation

Insertions/deletions

An extra nucleotide gets added or removed

- very bad b/c it causes a frameshift (shift in the reading frame)

Abnormal event can occur of expansion of trinucleotide repeats

Copy number increases

Example of expansion of trinucleotide repeats

Normally have 10 copies of CAG on chr. 8 = inc. to 200 copies

Abnormal DNA structure causes __________ to slip and copy section 2x

DNA polymerase

Anticipation

TNRE disorders usually get worse each generation

- Expansion grows = worse symptoms

How does DNA damage get converted into permanent mutations?

1) A change occurs in the structure of a nt (lesion/damage)

2) DNA rep occurs – DNA pol puts "wrong" nt across from the lesion

3) 2nd DNA rep occurs – Wrong nt serves as a template for complimentary wrong nt

Result: DNA now contains a completely wrong pair (cell sees as normal)

Causes of spontaneous damage

Errors of DNA polymerase

Some major causes of spontaneous errors during replication include

Strand slippage

Tautomeric shifts

Nitrogenous bases can exist in different chemical

forms called structural isomers

Example of tautomeric shifts

Abnormal T prefers to H bonds w/ G