ADL Lecture 5: 12.1-3; 13.5, 13.7

Question 1

Mutation frequency

Answer 1

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)

Question 2

Why are dominant mutations easier to detect than recessive mutations? How would you screen for each type?

Answer 2

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?

Question 3

Is there perhaps a particular chromosome/screening strategy where recessive mutations could easily by identified?

Answer 3

region-specific deletions via irradiation

Question 4

Say you already have a recessive allele at some gene, does this suggest a simple strategy for getting additional new mutations?

Answer 4

?

Question 5

Why might mutation frequency vary among organisms? among genes?

Answer 5

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.

Question 6

Loss of Function mutations (LOF)

Answer 6

(Null/ knockout mutations) complete gene inactivation

Question 7

Hypomorphic mutation

Answer 7

reduced expression of gene

Question 8

Hypermorphic mutation

Answer 8

increase gene expression

Question 9

Gain of Function mutation

Answer 9

qualitatively alters action of a gene (active in new tissues or binds new protein or DNA sequence)

Question 10

The Fluctuation Test

Answer 10

Luria/Delbruck

Determines whether mutations occur randomly or as an adaptation to environmental change.

Question 11

Random mutation hypothesis (fluctuation test)

Answer 11

predicts that the number of phage-resistant cells fluctuate substantially among populations as a result of random timing of mutation.

Question 12

Coding sequence mutations:

1. Silent
2. Missense
3. Nonsense
4. Frameshift

Answer 12

1. no change to amino acid sequence
2. changes one amino acid of the polypeptide
3. creates stop codon and prematurely terminates translation
4. results in wrong sequence of amino acids

Question 13

Regulatory mutations:

1. Promoter
2. Polyadenylation
3. Splice site

Answer 13

1. changes timing or amount of gene transcription
2. alters sequence of mRNA; may affect mRNA stability
3. May retain intron sequence in or exclude exon sequence from mature mRNA

Question 14

DNA replication mutation:

triplet-repeat expansion

Answer 14

increases (or less often, decreases) number of repeats of DNA triplets, causing instability of mRNA or incorrect number of repeating acids in a protein.

Question 15

Frameshift mutations

Answer 15

Insertion or deletion of one or more base pairs

Question 16

Regulatory mutations

Answer 16

affect regions such as promoters, introns, and regions coding 5’ UTR and 3’ UTR segments

Question 17

What are three types of regulatory mutations?

Answer 17

1. promoter mutations
2. mutations that impact splicing
3. cis-regulatory mutations

Question 18

Promotor mutation

Answer 18

• alter consensus sequence nucleotides of promoters (close to transcription start site)
• interferes with efficient transcription initiation

Question 19

Cryptic Splice sites

Answer 19

produce new splice sites that replace or compete with authentic splice sites during mRNA processing

Question 20

cis-regulatory mutations

Answer 20

• in regions of DNA to which cis-reg. transcription factors bind
• impact expression levels
• generally mild (because of redundancy)

Question 21

Are mutations impacting complex traits (heart disease, etc) more likely to be cis-regulatory mutations than coding?

Answer 21

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

Question 22

Spontaneous mutation

Answer 22

• 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

Question 23

DNA replication errors (slippage)

Answer 23

error rate due to slippage is higher than rate at which incorrect base are incorporated/nucleotides spontaneously change

Question 24

Trinucleotide repeat disorders (due to slippage)

Answer 24

wild-type alleles of the genes in question have a normal number of DNA trinucleotide repeats, whereas diseased individuals have much longer repeats

Question 25

Transposable genetic elements

Answer 25

DNA sequences that can move within the genome by an enzyme-driven process (transposition) (TEs are groups into “families”)

Question 26

insertional inactivation

Answer 26

a transposable element (TE) can cause a mutation if it inserts into a wild-type allele and disrupts its function

Question 27

Characteristics of Transposable genetic elements

Answer 27

transposition requires enzyme “transposase;” the gene for transposase is carried by some TEs
-some TEs carry genes that impart specific characteristics to cells or organisms

Question 28

What are the two groups of TEs in eukaryotes and what does each group do?

Answer 28

1. DNA transposons: transposed through a cut and paste mechanism
2. Retrotransposons: encode reverse transcriptase and traspose via RNA intermediate. (related to retroviruses)

Question 29

Non-LTR retrotransposons

Answer 29

subset of retrotransposons that lost their “long terminal repeat” (LTR). Includes LINE and SINE in humans. very common-higher in eukaryotes.

Question 30

DNA transposons

Answer 30

• transpose via cut and paste mechanism (TE is cleaved from one position in genome and same molecule is inserted somewhere else)
• target site duplication: characteristic of most TE insertions; results from asymmetrical cleavage
• have terminal inverted repeats
• encode transposase (enzyme that determines distance between cuts)

Question 31

LTR TEs

Answer 31

• posses terminal direct repeats (also called LTRs)
• copy via RNA intermediate
• have enzyme called reverse transcriptase (+ transposase) which can “reverse-transcribe” using RNA transcript as template for making complementary DNA daughter strand

Question 32

Transposable elements (TEs)

Answer 32

-genomes of most organisms contain multiple copies of each “family” of TEs
-TEs can persist for long periods/ undergo mult. mutational changes
~~45% human genome consists of TEs