THEME 4 MOD 4 Flashcards
Why are changes in genetic information important?
- affect protein structure and function
- cause devastating cellular consequences
- can be beneficial mutations
- responsible for large array of genetic differences among organisms
- considered to be the source of genetic variation
How can mutations occur?
- due to environmental factors, spontaneous mutations (most common)
- errors during dna replication: errors at nucleotide level (eg improper base pairing) can be corrected, but if they aren’t, can lead to improper template sequences which propgate the mutation to daughter strands
How common are nucleotide mutations?
- very rare
- most animals have very low probability rate of a specific nucleotide mutation occurring during a round of replication, however viruses have a high mutation rate, specifically rna viruses
Why do rna viruses have a high mutation rate?
- delicate rna backbone leading to common breakages and damage
- rna genomes have no proofreading mechanisms
Gentic mutations in human cells
- occurs in germline or somatic cells
- in somatic cells: mutation will be progenitor of population of mutated identical daughter cells, leading to a patch or region of cells with that mutation.
- The earlier a somatic cell mutation occurs in the developmental cascade, the more widely spread it will be and the larger the spread of the mutated genome will be throughout the body
- somatic mutations are never passed on to progeny, only germline mutations where every cell in the embryo will have this mutation
When is a mutation largely negligable?
- when it occurs in a somatic cell suspended in the post-mitotic g0 phase or is no longer dividing
joshua and esther lederberg experiment (1952) and application
- grow bacteria colonies non selectively on agar
- stamped (also called replica plating, preserves arrangement of colonies) original colonies on cloth and stamped into another dish with penicillin (antibiotic) in agar
- only a few colonies survived, hypothesized that these colonies had a mutation making them resistant to penicillin
- need to know: was antibiotic resistance evolved or was there a genetic mutation
- isolated suspected mutant colony from the original colony and cultured the cells in penicillin
- found they had cultured a pure antibiotic resistant culture
- mutation that confers antibiotic resistance existed prior to exposure to penicillin, mutations can create random beneficial changes
Why is it important cells have mechanisms to detect mutations and repair them?
mutations can lead to cell death, cancer, aging, disease
Other than mutations in dna replication, how can mutations occur (external factor)
mutagens and agents including radiation and chemicals can induce mutations
How is dna damage corrected?
specialized repair enzymes
dna ligase: repairs breaks in backbone, specialize in single strand repair
Dna polymerase: proofreading
nuclease: Dna cutting enzyme, single stranded cleavage of the back bone some distance away from mismatched nucleotides (create a kink in backbone detectable by repair enzymes)
enzyme removes nucleotides of cleaved strand
dna polymerase and dna ligase will then refill/close the gap through dna synthesis to create a complete dna strand
Base excision repair
- uracil in dna signals need for repair
- dna uracil glycosylase enzyme cleaves uracil from back bone by itself
-AP endonuclease detects missing base, cleaves the backbone on either side of the gap - dna ligase and dna polymerase synthesize appropriate base pair
Nucleotide excision repair
- enzymes remove and replace multiple mismatches, cleaving the backbone around the area “flanking the area”
- dna ligase and polymerase fill in the gap
small scale point mutations
- usually a single nucleotide mismatch during dna replication, if escapes the repair mechanisms, it will become a permanent part of the genome
SNPs
single nucleotide polymorphisms, a single nucleotide pair improperly replaced by an incorrect base pair
are point mutations always detrimental
no, some go undetected with no effect on structure and cell function, others are detrimental
sickle cell anemia
- single nucleotide mutation that is non-synonymous or missense
- causes translation of valine aa instead of glutamate
- this mutation of the beta globin sequence causes hemoglobin to have a reduced ability to bind oxygen
- while some mutations in protein coding regions improve the proteins function, most often these mutations lead to less functional or useless proteins
What is a silent or synonymous mutation
-when a change in nucleotide pair leads to the codon still coding for the same amino acid
- think of redundancy of genetic code
nonsense mutation
single nucleotide mismatch turns a codon into a premature stop codon resulting in a shorter polypeptide sequence which impairs the structure and function of the protein
all point mutation types
- single nucleotide substituions
- insertions: one or more extra nucleotide is inserted into synthesized dna
- deletions: skipping or removal of nucleotide during replication
degree of impact of 2 and 3 depends on size
example of deletion
- 3 codon deletion of protein coding for chlorid channels causes cystic fibrosis
- most cftr transport proteins are degraded before reaching the cell membrane
- proteins cant properly transport chloride ions out of the cell and develop a thick sticky mucus, most patients succumb to the disease through bacterial infection or respiration malfunction
frameshift mutations
- insertion or deletion mutations not in multiples of three that lead to improper codons down stream of the insertion or deletion
- can cause massive missense mutation resulting in premature termination
- proteins of frameshift mutations are almost always non functional
chromosomal mutations (large point mutations)
deletions, duplications, inversions, and reciprocal translocations
chromosomal mutations: deletion
- chromosomal fragment is lost, loss of genes is likely
- centromere deletion can cause chromosome to be lost in a few cell division because it cannot be properly allocated to the poles of the dividing cell
- deletion of segment of chromosome in a homologous pair in diploid organism: may or may not persist depending on whether the other chromosome can compensate and provide for enough of the gene product
- chromosomal deletions in embryo lead to embryo death or fatal abnormalities
chromosomal mutations: duplication
- small duplications are largley harmless
- having extra copy of a gene can be advantageous and/or lead to a new gene being formed (called duplication and divergence)
