Final Flashcards
What are lethal genes?
Genes which result in the reduction of viability of an individual or become a cause for death of individuals carrying them - they are usually a result of mutations in genes that are essential for growth or development
Describe study by Lucien Cuenot – how were lethal genes first discovered?
The agouti gene in mice is largely responsible for determining coat color
– The wild-type allele (A) produces a blend of yellow and black pigmentation in each hair of the mouse – this yellow and black blend may be referred to as ‘agouti’ in color
– One of the mutant alleles (AY) of the agouti gene results in mice with a much lighter, yellowish color
1) When two homozygous wild-type agouti mice were crossed, only agouti offspring were obtained (which was expected)
• When yellow mice were crossed with homozygous wild-type agouti mice, a 1:1 phenotypic ratio of yellow and agouti offspring were obtained
– This indicated that the yellow mutation is dominant, and all the parental yellow mice were heterozygous for the mutant allele ( AYA)
- Instead, he observed a 2:1 phenotypic ratio of yellow to agouti mice
2) By mating two yellow mice, Cuénot expected to observe a usual 3:1 phenotypic ratio of yellow to agouti
- Instead, he observed a 2:1 phenotypic ratio of yellow to agouti mice
– After many genetic crosses, he was unable to produce any mice that were homozygous for the yellow allele
- As it turned out, this unusual ratio reflected that some of the mouse embryos (homozygous AYAY genotype) died very early in development, long before birth
What are recessive lethals and give examples
These are most common type of lethal genes, and their expression occurs in homozygous conditions only, hence survival of heterozygous ones are unaffected
• They are a pair of identical alleles that results in the death of an
entity ultimately
• Despite the fact that recessive lethals can code for recessive or dominant characteristics, they turn fatal only under homozygous conditions
– Examples involving recessive lethals that code for dominant traits = Manx cats, yellow coat color in mice, creeper chickens
– Example involving recessive lethals that code for recessive traits = sickle cell anemia, cystic fibrosis
What are dominant lethal genes and provide an example?
Lethal genes which reduce viability even in heterozygotes, are said as dominant lethals
• These are the alleles whose presence is required in one copy in an entity for them to turn fatal
• The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote
– These alleles are not commonly found in populations because they usually result in the death of an organism before it can transmit its lethal allele on to its offspring – This allele can only be transmitted if the lethality phenotype occurs after reproductive age
EXAMPLE: Huntington’s disease
– Huntington’s disease is a rare neurodegenerative disorder that ultimately results in death
– This disease is due to a dominant autosomal allele ( H), where the onset of the disease in heterozygotes (Hh) is delayed, usually well into adulthood
What are conditional lethals and give an example of
These alleles turn deadly only when there is an external environmental aspect involved
• EXAMPLE: Favism
– A sex-linked inherited condition that causes the carrier to develop hemolytic anemia when they eat fava beans
o Hemolytic anemia = a condition in which red blood cells break apart and block blood vessels
o Blockage can cause kidney failure and result in death
- Results from deficiency in an enzyme called glucose-6-phosphate dehydrogenase (G6PD)
What does each nucleotide consist of?
• Phosphate group
• Deoxyribose sugar group
• Nitrogen-containing base
What are the four kinds of bases in DNA?
Pyrimidines: one single ring, with 6 members and 2 nitrogen atoms
- Utracil
- Thymine
- Cytosine
Purines: two-ringed structure with 9 members and 4 nitrogen atoms
- Adenine
- Guanine
Useful mnemonic
PURE As Gold
CUT the PYE
What are the parts of a DNA (structure/bonds, etc)
DNA is a double-stranded helix
Strands are antiparallel to each other
– The two strands run side by side to each other but in opposite directions – The 5’ end has a free phosphate group while the 3’ end has a free hydroxyl (OH) group
• One turn of the helix occurs every 10 base pairs
• Negatively charged phosphate groups face out (making DNA hydrophilic overall)
- Important bonds that hold the structure – hydrogen bonds between nucleotide bases and phosphodiester bonds between the 5-carbon sugar backbone
Complementary base pairing (Watson-Crick):
– Thymine and adenine (2 hydrogen bonds)
– Cytosine and guanine (3 hydrogen bonds)
What is an origin of replication?
• Origin of replication = DNA sequence where replication is initiated
• A replication bubble is formed (each bubble has two replication forks)
• A eukaryotic chromosome may thousands of replication origins, bacterial chromosomes have a single origin of replication
What is the mechanism and proteins in DNA replication
– DNA helicases unwind the double helix by breaking hydrogen bonds between strands
– Single-stranded DNA binding proteins prevent DNA strands from rejoining after helicase separates strands
– The initial nucleotide strand is an RNA primer (RNA primase catalyzes the synthesis of short RNA primers)
– DNA replication is catalyzed by DNA polymerase III which needs an RNA primer
– DNA polymerase I degrades the RNA primer and replaces it with DNA nucleotides (synthesized in 5’-
to-3’ direction, reads this template strand in a 3’-to-5’ direction - has proofreading activity)
– DNA ligase joins the short DNA fragments on lagging strand (Okazaki fragments) into a continuous daughter strand (introduces a phosphodiester bond between two fragments)
– Topoisomerase binds to DNA and relieves torsional stress experienced further upstream along helix that occurs as a result of unwinding due to helicase activity (cuts phosphodiester bond from one or both strands of double helix to relax DNA, and then cut strand(s) is/are reannealed
What is the leading vs lagging strand?
Leading strand: continuous synthesis
- the leading strand is synthesized continuously in the 5’-to-3’ direction (new strand) by DNA polymerase, starting from 3’ end of original
Lagging strand: discontinuous synthesis
- synthesized discontinuously starting from 3’ end of original, primase synthesizes a short RNA primer which is extended by DNA polymerase to form an Okazaki fragment
- DNA ligase joins the Okazaki fragments
What was the Fredrick Griffith Experiment?
- Experiment involved the use of two strains of the pneumococcus bacterium: One strain of bacteria had a smooth polysaccharide capsule (also known as the “smooth” strain) that is essential for infection while the other (“rough” strain) did not have a capsule
• Injection with live encapsulated bacteria (virulent form: S strain) – mice contracted
pneumonia and died
• Injection with live naked bacteria (non-virulent form: R strain) – mice lived
• Injection with heat killed encapsulated bacteria – mice remained healthy
• Injection with heat killed encapsulated bacteria and live naked bacteria – mice contracted pneumonia and died - conclusion: a chemical substance from one cell is capable of genetically transforming another cell
What was Oswald Avery’s Experiment
Decided to identify specific molecules that could transform non-encapsulated bacterium into encapsulated form – In a significant departure from Griffith’s procedure, however, Avery’s team employed a method for transforming bacteria in cultures rather than in living mice, which gave them better control of their experiments
1) heat-killed virulent S strain filtrated treated with enzymes that either destroy RNA, proteins, or DNA
2) the treated samples were added to cultures of R strain bacteria.
- cultures treated with RNase or protease contain transformed S strain bacteria.. ..but the culture treated with DNase does not.
CONCLUSION: Because only DNase destroyed the transforming substance, the transforming substance is DNA
What was the Hershey-Chase Experiment?
Wanted to confirm if DNA is the carrier of genetic material based on the findings by Avery
– Experiments involved the T2 bacteriophage, a virus that infects E. coli bacterium
o Use radioisotopes to trace the fate of phage’s protein and DNA:
1) Experiments begins with culturing of viruses in two types of medium
– One set of viruses was cultured in medium of radioactive sulfur ( 35S) – which would incorporate
into the phage protein
– Other set of viruses was cultured in medium of radioactive phosphorous (32P) – which would
incorporate into the phage DNA
2) The radioactively labelled phages were allowed into infect E. coli bacterial cells in separate flasks – After attachment of a phage to E. coli the phage DNA will enter cytoplasm of bacterial cell
• The infected E. coli cell cultures are agitated through blending to separate the phage viral coats (or phage “ghosts”) from the bacterial cells
• Centrifugation allows for separation of the pellet (containing the bacterial cells)
from the supernatant (containing the phages)
• 32P is discovered within the bacterial pellet whereas 35S is discovered in the
supernatant where the phage viral coats are found
• CONCLUSION: Injected DNA of the phage provides genetic information
What are the three postulated mechanisms of DNA replication:
Conservative: both strands of the daughter double helices contained new material
Semi-conservative: each daughter double helix contained one parent strand and one new strand (so total of two strands after replication)
Dispersive: results in two DNA molecules that are mixtures/hybrids of parental and daughter DNA
