Genetics Exam 4

Lecture 19-23

Mutation

Alteration in DNA sequence (not RNA)

• Base pair substitution

• Base pair deletion

• Base pair insertion

• Major alteration in chromosomal structure

Where may mutations occur?

Somatic cells and germ cells

Coding or noncoding regions

Are mutations always bad?

No, they are a source of genetic variation

How are mutations useful for probing fundamental biological processes?

By knowing the phenotype and gene, you can understand the role of a sequence

Point mutation and base substitution

Transitions and transversions

Transitions

Pyrimidine replaces pyrimidine or purine replaces purine

Transversion

Purine and pyrimidine are interchanged

Missense

Results in new triplet code for a different amino acid

Nonsense

Results in triplet code for stop codon

• UAA, UGA, UAG

Silent

New triplet code still codes for same amino acid

Sickle cell disease** EXAM

Strikes individual with two copies of the sickle-cell allele

• Allele affects structure and function of hemoglobin, reducing the oxygen carrying capacity of red blood cells

• Homozygous individuals = lethal

• Heterozygotes = more likely to survive malaria, less harmful effects

** Why does it happen

** Why can it be beneficial

Reading frame

Triplets

Frameshift mutation

• Deteltion and insertion

• Loss or addition of nucleotide causes shift in reading frame

• Alters the entire amino acid sequence that follows the mutation

Which statement is false about mutation?

Nonsense mutations have no effect on the amino acid produced by a codon because of redudancy in the genetic code

Forward mutation

Wild type to mutant type

Reverse mutation

Mutant type to wild type

Supressor mutation

Occurs at a different site from the original mutation. Hides or suppresses the effect of another mutation

• Intragenic

• Intergenic

Intragenic

An intragenic suppressor mutation occurs in the gene containing the mutation being suppressed

Intergenic

Occurs in a gene other than the one bearing the original mutation that it suppresses

A mutation in gene X overrides the effect of a previous mutation in gene Y and restores the wild-type phenotype

Intergenic suppressor

Neutral mutation

No change in function. Does not affect an organism’s fitness. Focuses more on the phenotype

Are types of mutation mutally exclusive?

No

Lethal

Disrupt essential process and results in death

Lethal Conditional

• Dependent on organism’s environment

• Temperature sensitive

Favism

• Hemolytic anemia in fava beans

• Hemolytic anemia after eating fava beans or being exposed to the pollen of the plant

• Example of lethal conditional mutation** EXAM

Dominant-negative mutations **confusing

Disrupt the activity of the wild-type gene when eoverexpressed

• Neg: expression of a mutant protein interferes with the activity of a wild-type protein

• Dom: only one copy of the gene needs to be mutated to cause a disease phenotype

Somatic cells

Sex cells

• Sperm: 22 autosomes, x or y

• Unfertilized egg (ovum): 22 autosomes + x

Diploid

Haploid

How many chromosome pairs?

23 (46 chromosomes)

• 23 in sex cells: 22 autosomes

Autosomes

Homologous

Consequence of sexual reproduction

Are somatic mutations in any cell except germ cells heritable?

No

Are germ-line mutations in gametes inherited?

Yes

Autosomal mutations

Occurs within genes located on autosomes

X and Y linked mutations

Occur within genes located on X and Y chromosomes, respectively

Spontanwous mutation

• Changes in nucleotide sequence that occur naturally

• Arise from normal biological or chemical processes

• Low rate

Spontatneous replication errors

• Replication is imperfect

• DNA pol. occasionally inserts incorrect nucleotides

• Misincorporated nucleotides persist after proofreading

Proofreading

Fixing mis-paired bases during DNA synthesis/replication by DNA polymerases

Repair

Right after DNA replication or detect and correct damage throughout the cell cycle

Mispairing errors predominantly lead to ___ mutations

Point

Tautomeric shifts

• Spontaneous replication errors

• Causes transition mutation in the complementary strand

• Can change the bonding structure, allowing noncomplementary base pairing

Tautomers

Two molecules with the same moleculart formula but different connectivitiy

Noncomplementary base pairing

• Increase chance of mispairing during DNA replication

• May lead to permanent base-pair changes and mutations

Mutations are either ___ and ___

Spontaneous, induced1

Spontaneous mutations include

Spontaneous replication errors and spontaneous chemical changes

What are spontaneous chemical changes?

Depurination: loss of purine leading to an apurinic site

Deamination: loss of an amino group

Where do depurination and deamination take place?

Double-helical DNA

Depurination and deamination do not break the _____ ____

Phosphodiester backbone

What can depurination lead to if uncorrected?

Loss of