ADL Lecture 5: 12.1-3; 13.5, 13.7 Flashcards
DNA mutagenesis and repair, I (types of mutations and TEs)
Mutation frequency
Frequencies per gene are low in all genomes but differ among species/genes within species.
of mutational events in given gene/ Time
Recessive mutations are more common than dominant (but dominant are easier to screen for)
Why are dominant mutations easier to detect than recessive mutations? How would you screen for each type?
Dominant mutations are easier to detect because it only takes one allele dominant allele to portray sepcific phenotype. Complementary dominant genotypes may also play a role in this.
-screen for each type?
Is there perhaps a particular chromosome/screening strategy where recessive mutations could easily by identified?
region-specific deletions via irradiation
Say you already have a recessive allele at some gene, does this suggest a simple strategy for getting additional new mutations?
?
Why might mutation frequency vary among organisms? among genes?
The nature of the gene and its environment can influence the mutation rate. The size of the gene, its base composition, its position in the genome, and whether or not it is being actively transcribed influence its mutation rate.
Loss of Function mutations (LOF)
(Null/ knockout mutations) complete gene inactivation
Hypomorphic mutation
reduced expression of gene
Hypermorphic mutation
increase gene expression
Gain of Function mutation
qualitatively alters action of a gene (active in new tissues or binds new protein or DNA sequence)
The Fluctuation Test
Luria/Delbruck
Determines whether mutations occur randomly or as an adaptation to environmental change.
Random mutation hypothesis (fluctuation test)
predicts that the number of phage-resistant cells fluctuate substantially among populations as a result of random timing of mutation.
Coding sequence mutations:
- Silent
- Missense
- Nonsense
- Frameshift
- no change to amino acid sequence
- changes one amino acid of the polypeptide
- creates stop codon and prematurely terminates translation
- results in wrong sequence of amino acids
Regulatory mutations:
- Promoter
- Polyadenylation
- Splice site
- changes timing or amount of gene transcription
- alters sequence of mRNA; may affect mRNA stability
- May retain intron sequence in or exclude exon sequence from mature mRNA
DNA replication mutation:
triplet-repeat expansion
increases (or less often, decreases) number of repeats of DNA triplets, causing instability of mRNA or incorrect number of repeating acids in a protein.
Frameshift mutations
Insertion or deletion of one or more base pairs
Regulatory mutations
affect regions such as promoters, introns, and regions coding 5’ UTR and 3’ UTR segments
What are three types of regulatory mutations?
- promoter mutations
- mutations that impact splicing
- cis-regulatory mutations
Promotor mutation
- alter consensus sequence nucleotides of promoters (close to transcription start site)
- interferes with efficient transcription initiation
Cryptic Splice sites
produce new splice sites that replace or compete with authentic splice sites during mRNA processing
cis-regulatory mutations
- in regions of DNA to which cis-reg. transcription factors bind
- impact expression levels
- generally mild (because of redundancy)
Are mutations impacting complex traits (heart disease, etc) more likely to be cis-regulatory mutations than coding?
more likely to be a cis-regulatory mutation: a sequence or regulatory protein that is part of the same DNA molecule as the gene of interest
Spontaneous mutation
- arise in cells without exposure to agents capable of inducing mutation
- arise primarily through errors in DNA replication or spontaneous changes in chemical structure of nucleotide base
DNA replication errors (slippage)
error rate due to slippage is higher than rate at which incorrect base are incorporated/nucleotides spontaneously change
Trinucleotide repeat disorders (due to slippage)
wild-type alleles of the genes in question have a normal number of DNA trinucleotide repeats, whereas diseased individuals have much longer repeats
