bio 207 8 and 9
what does radiation increase
Radiation greatly increases mutation rates in all organisms.
Pyrimidine dimer
two thymine bases covalently bind and block DNA replication.
DNA Repair Mechanisms:
Translesion Polymerases
What is the SOS system in bacteria?
The SOS system allows bacterial cells to bypass replication blocks through a mutation-prone pathway.
What does DNA polymerase η (eta) do in eukaryotes?
DNA polymerase η (eta) replaces damaged DNA with AA in eukaryotic cells to bypass replication blocks.
What do high-energy radiations (X-rays, gamma-rays, cosmic rays) do to DNA?
They remove electrons from atoms, altering the chemical structure of bases and causing double-stranded DNA breaks.
What effect does UV radiation have on DNA?
UV radiation causes pyrimidine dimer formation (usually TT, but also TC/CC), which stalls or stops DNA replication.
What is the role of the SOS system in bacteria?
he SOS system bypasses pyrimidine dimers during DNA replication, but at a high error rate.
Why would a cell want to bypass replication blocks?
To prevent cell death and survive DNA damage, even though it increases the risk of mutations. Bypassing blocks allows replication to continue under stress, though it’s error-prone.
What are double-stranded breaks in DNA?
Double-stranded breaks (DSBs) are when both strands of the DNA helix are severed, which can lead to significant damage. They can be caused by high-energy radiation (X-rays, gamma-rays) or certain chemicals and pose a risk to the integrity of the genome.
what is a historical event that lead to many somatic muatiosn in survivors
Hiroshima was destroyed by an atomic bomb inn
1945.
What were the effects of the atomic bomb's radiation on survivors?
Survivors of the initial blast suffered from radiation sickness and somatic mutations, most commonly leading to leukemia.
Were there increased germline mutations in the children of atomic bomb survivors?
Estimates showed no increased germline mutations, likely because those with the highest exposure did not survive.
What are base analogs and how do they cause mutations?
Base analogs are chemicals that resemble DNA bases in structure. When incorporated into DNA, they can lead to incorrect base pairing and cause mutations.
What are alkylating agents and give an example?
Alkylating agents donate alkyl groups (like a methyl or ethyl group) to DNA, causing mutations. An example is Ethylmethylsulfonate (EMS) and mustard gas, which was used in WWI chemical warfare (now banned).
How does deamination cause mutations?
Deamination, caused by chemicals like nitrous acid, removes an amine group from a base, altering its pairing ability and leading to mutations.
What is the effect of hydroxylamine on DNA?
Hydroxylamine adds a hydroxyl group to bases, causing changes in base-pairing that can lead to mutations.
How do oxidative reactions contribute to mutations?
Oxidative reactions, like those caused by superoxide radicals or hydrogen peroxide, can damage DNA by altering base structures, leading to mutations.
What are intercalating agents and how do they cause mutations?
Intercalating agents like proflavin, acridine orange, and ethidium bromide insert themselves between DNA bases, causing frameshift mutations during DNA replication.
What is 5-Bromouracil and how does it function as a base analog?
5-Bromouracil resembles thymine, but it has a bromine atom in place of the methyl group on the 5-carbon atom. It can cause mutations by incorrectly pairing with adenine instead of guanine during DNA replication.
What is 2-aminopurine and how does it function as a base analog?
2-Aminopurine resembles adenine but has an amino group at the 2-position. It can pair with thymine or cytosine, causing mutations by mispairing during DNA replication.
Incorporation of 5-bromouracil into a DNA
strand can lead to a replicated error, how?
if 5-bromouracil is incorporated into DNA in place of thymine, it may mispair with guanine in the next round of replication, the next replication this G pairs with C leading to permamnent muation, if it pairs with A then no replicated error occurs.
basically incorporation of bromouracil followed by mispairing leads to a TA--> CG transtion mutation
what type of muations does EMS/alkylation cause
transition mutation during DNA replication
CG--> TA
TA--> CG
what type of mutation does nitrous acid (HNO2)/deamination cause
Nitrous acid (HNO₂) causes deamination of cytosine, converting it into uracil. During DNA replication, uracil pairs with adenine instead of guanine, leading to a transition mutation (cytosine to thymine) after several rounds of replication.
CG-->TA
TA-->CG
what type of mutation does hydroxylamine (NH2OH)/hydroxylation cause
hydroxylamine (NH₂OH) adds a hydroxyl group to cytosine, converting it into hydroxycytosine. This altered base mispairs with adenine instead of guanine, leading to a transition mutation (cytosine to thymine) during DNA replication. only CG-->TA way not vice versa
C-->T
G-->A
How does EMS (ethylmethane sulfonate) cause mutations?
EMS is an alkylating agent that adds an ethyl group to normal nucleotides, resulting in mis-pairing during DNA replication. This causes point mutations, such as G→A or C→T transitions.
How do oxidative radicals affect guanine?
Oxidative radicals convert guanine into 8-oxy-7,8-dihydrodeoxyguanine, which can mispair with adenine during DNA replication, leading to G→T transversions.
What is the difference between a transversion and a transition mutation?
Transition: A mutation where a purine (A or G) is replaced by another purine, or a pyrimidine (C or T) is replaced by another pyrimidine (e.g., A→G or C→T).
Transversion: A mutation where a purine is replaced by a pyrimidine, or a pyrimidine is replaced by a purine (e.g., A→C, G→T).
How do intercalating agents like proflavin and acridine orange cause mutations?
Intercalating agents insert themselves between adjacent bases in the DNA, distorting the helix's three-dimensional structure. This leads to insertions and deletions during DNA replication, causing frameshift mutations.
How do we test chemicals to identify mutagens?
The Ames test uses his⁻ strains of bacteria to test chemicals for their ability to cause his⁻ to his⁺ mutations. Since mutagenic activity is closely linked to carcinogenic potential, the Ames test is widely used to screen chemicals for their cancer-causing ability.
How are the bacteria prepared for the Ames test?
the test uses his⁻ strains of bacteria (bacteria that cannot grow without histidine) that have been genetically modified to be sensitive to mutations.
What is the first step in the Ames test?
The first step is to expose the his⁻ bacteria to the chemical being tested, along with a plate containing minimal histidine, which allows only bacteria with mutations that restore their ability to make histidine to grow.
What happens if the chemical causes a mutation in the bacteria during the Ames test?
If the chemical causes mutations, some his⁻ bacteria will mutate to his⁺, meaning they can now make histidine and grow. The number of his⁺ colonies indicates the mutagenic potential of the chemical.
How do we determine if a chemical is a mutagen in the Ames test?
A higher number of his⁺ colonies compared to a control (untreated) sample indicates that the chemical is mutagenic and may have carcinogenic potential.
Why is the Ames test useful in cancer screening?
Since mutagenic chemicals are often carcinogenic, the Ames test serves as a fast, preliminary screening method to identify chemicals that could potentially cause cancer.
How is EMS (ethylmethane sulfonate) used in forward genetic screens?
EMS is an alkylating agent that induces point mutations in the genome. In forward genetic screens, it is used to create mutations in a population of organisms. Researchers then observe the phenotypes and use these to identify genes involved in specific biological processes or traits.
What is the goal of forward genetic screens?
Forward genetic screens aim to identify genes that contribute to a specific phenotype or trait by inducing mutations and observing the resulting changes in the organism's traits.
What is the problem researchers face after conducting a genetic screen?
After a genetic screen, researchers have a collection of new mutants, but they don’t know if the same genes have been mutated multiple times in different individuals.
What is the role of complementation tests in forward genetic screens?
Complementation tests are used to determine if mutations in different mutants affect the same gene. If two mutants with the same phenotype complement each other, they are in different genes. If they don’t complement, they are likely mutations in the same gene.
How can you identify genes necessary for learning and memory?
1. Forward Genetic Screen: Use mutagenesis (like EMS) to create mutations in a population of organisms, then observe how these mutations affect learning and memory behaviors.
2. Behavioral Assays: Test the organism for learning and memory tasks (e.g., maze learning, fear conditioning) to identify mutants with impaired learning.
3.Gene Identification: Once mutants are found, use genetic mapping or next-generation sequencing to identify the specific genes involved.
4.Complementation Tests: If multiple mutants share similar learning defects, perform complementation tests to determine whether mutations are in the same or different genes.
5.Gene Expression Analysis: Analyze the expression of candidate genes in the brain during learning-related tasks to confirm their involvement in memory processes.
How can you identify genes necessary for learning using EMS mutagenesis?
1.Feed EMS to male flies and allow them to mate.
2.Take the progeny and establish heterozygous +/m stocks (~200 progeny).
3.Test homozygous m/m flies for learning ability.
4.Keep stocks where homozygotes show poor learning (e.g., 10% of stocks = ~20 lines).
5.Two extreme possibilities:
Extreme I: 20 mutations in 20 different genes.
Extreme II: 20 mutations in the same gene.
How do complementation tests work to determine if mutations are in the same gene?
purpose: Determine if two mutations (e.g., m1, m2, ...) are alleles of the same gene.
Procedure:
1.Cross m1/+, m2/+, and m3/+ heterozygotes with wild-type alleles.
2.All heterozygotes (e.g., m1/+, m2/+, m3/+) show wild-type phenotypes (normal learners).
3.Homozygotes (m1/m1, m2/m2, m3/m3) show similar poor learning phenotypes.
If two mutations produce normal phenotypes when crossed, they are likely in different genes (complementation). If they don’t, they are likely mutations in the same gene.
Do mutations m1 and m2 occur in the same gene?
1.Cross the parental m1/m1 and m2/m2 mutants.
2.F1 progeny: Test for learning ability.
3.If F1 progeny are still poor learners, this indicates that m1/m2 do not complement, meaning they are likely mutations in the same gene.
Conclusion: m1/m2 mutations fail to complement, suggesting they are alleles of one gene.
Do mutations m1 and m3 occur in the same gene?
1.Cross the parental m1/m1 and m3/m3 mutants.
2.F1 progeny: Test for learning ability.
3.If F1 progeny are normal learners, this indicates that m1/+ and +/m3 complement each other.
Conclusion: Since the mutant phenotypes complement, m1 and m3 are mutations in two different genes, not alleles of the same gene.
How do complementation groups help identify mutations in the same or different genes?
1.Test crosses are done between multiple mutant lines (e.g., m1, m2, m3, ... m6).
2.The results show whether the mutations complement (normal learners) or fail to complement (poor learners).
3.Based on the cross results, you group mutants into complementation groups:
-Complementation group I: m1, m2, m5 (mutations in the same gene).
-Complementation group II: m3 (mutation in a different gene).
-Complementation group III: m4, m6 (mutations in another gene).
Conclusion: There are 3 complementation groups, indicating mutations in 3 different genes.
What would be the likely hair color of an F1 offspring from a cross between Solomon Island blonde and Swedish blonde hair types?
-Solomon Island blonde has TYRP1- and KITLG mutations.
-wedish blonde has TYRP1- and KITLG+.
The F1 would likely NOT have blonde hair because of the genetic interactions between TYRP1 and KITLG.
F1 offspring could have brown or black hair, depending on the influence of other genes involved in hair color.
How can rescue by complementation help identify which mutation (Gene A or Gene B) causes poor learning in m3?
Problem: m3 has mutations in both Gene A and Gene B, and both cause non-functional products.
Solution: Perform complementation tests to rescue one mutation at a time.
-Cross m3 with a strain that has a functional Gene A or Gene B.
-If the m3 mutation is rescued by a functional copy of Gene A, the poor learning phenotype is likely due to the Gene B mutation.
-If m3 is rescued by a functional copy of Gene B, the poor learning phenotype is likely due to the Gene A mutation.
Conclusion: This allows you to identify which gene mutation is responsible for the poor learning phenotype.
How can rescue by complementation using genetic engineering identify which gene mutation causes poor learning in m3?
1.Introduce a wild-type copy of Gene A into the m3 fly strain.
2.Test transgenic flies for learning ability:
-If m3 flies become normal learners, the mutation in Gene A is responsible for poor learning.
-If m3 flies are still poor learners, the mutation in Gene A is NOT responsible.
3.Next, perform a rescue complementation experiment with a wild-type copy of Gene B to test if Gene B is responsible for the poor learning phenotype.
4.The gene responsible for poor learning is identified based on which rescue experiment restores normal learning.
how do transposable elements work
if there are staggered cuts in the target dna, transposable element can insert itself into the dna, the staggered cuts leave short single stranded pieces of DNA, the replication of this single stranded DNA creates the flanking direct repeats
What are transposable elements?
Transposable elements are parasitic DNA sequences that can move within the genome, often causing mutations.
What is transposition?
Transposition is the movement of transposable elements from one location to another within the genome.
What are the key features of transposable elements?
(2)
Flanking direct repeats: Short sequences that are repeated on both sides of the transposon.
Terminal inverted repeats: Sequences that are reversed and complementary at the ends of the transposon.
How can transposition occur?
Transposition can occur through DNA or an RNA intermediate.
What is replicative transposition?
In replicative transposition, a new copy of the transposable element inserts into a new location, while the old copy remains at the original site.
What is nonreplicative transposition?
In nonreplicative transposition, the old copy excises from its original site and moves to a new site, leaving no copy behind.
What is RNA intermediate transposition?
RNA intermediate transposition requires reverse transcription to convert the RNA back into DNA before integrating into the target site.
What are the two types of intermediates involved in transposition?
DNA or an RNA intermediate.
What happens during replicative transposition?
A new copy of the transposable element inserts into a new location, and the old copy remains at the original site.
What happens during nonreplicative transposition?
The old copy excises from its original site and moves to a new site, leaving no copy behind.
What is involved in RNA intermediate transposition?
RNA intermediate transposition requires reverse transcription to convert the RNA into DNA before it integrates into the target site.
What percentage of the human genome is made up of transposable element sequences?
About 45% of the human genome comprises sequences related to transposable elements, mostly retrotransposons.
How do transposons cause mutations?
Transposons cause mutations by:
Inserting into another gene, disrupting its function.
Promoting chromosomal rearrangements (e.g., inversions, deletions).
Moving genes (deleting and inserting) as they move within the genome.
how can transposition lead to deletion
pairing by looping and crossing over between two transposable elements oriented in the same direction leads to deletion
how can transposable elements lead to inversion
pairing by bending and crossing over betwen two transposable elements oreinted opposite direction leads to inversion
How do transposons contribute to chromosomal rearrangements?
Transposons can cause chromosomal rearrangements by:
Inserting at new locations, disrupting the normal structure of chromosomes.
Promoting inversions, deletions, or duplications in the genome as they move.
how can transpositon lead to one chromosme with deletion and one chromosome with duplication
misalignment and uneqal exchnage between transposable elements located on sister chromatids
What are insertion sequences like IS1 in bacteria?
Insertion sequences (e.g., IS1) are simple transposable elements found in bacteria. They consist of:
Short DNA sequences that can move around within the genome.
transposase gene, then Typically include 23bp terminal inverted repeats and 9bp flanking direct repeats.
They do not carry additional genes, only the genes required for transposition.
What is the structure of Tn10, a composite transposon in bacteria?
Tn10 has the following structure:
Two IS elements (IS10) at the ends: These are insertion sequences that mediate transposition.
Central region: Contains genes, such as antibiotic resistance genes (e.g., tetracycline resistance).
The IS10 elements are identical or nearly identical, enabling the movement of the central region between different genomic locations.
flanking direct repeat seuqences on the outside
Who was the first to discover transposable elements?
Barbara McClintock was the first to discover transposable elements in the 1940s while studying maize (corn). She identified that certain genes could move around within the genome, causing changes in the expression of other genes.
What are Ac and Ds in maize?
Ac (Activator) and Ds (Dissociation) are transposable elements in maize discovered by Barbara McClintock.
Ac is an autonomous element, meaning it can move on its own because it encodes the necessary transposase enzyme.
Ds is a non-autonomous element, meaning it cannot move on its own but relies on Ac for transposition.
How does transposition result in variegated maize kernels?
Transposition causes variegated maize kernels by disrupting the C (color) gene in maize.
Ac element produces transposase which stimulates transposition of a Ds element in the C allele. this disrupts its pigment producing function, resulting cells have genotype Ctc and are colorless
Variegation occurs because some kernels have the C gene active (producing color), while others have the gene disrupted by the transposon, leading to a lighter color or no color at all.
how can theri be mosaic tranpostion
an Ac element produces transposase which stimulates further transpositon of the DS element in some cells. As DS transposases, it leaves the C alle restoring alleles function. A cell in which Ds has transposed out of the C allele will produce pigment generating spots of color in an otherwise colorless kernel
What are the characteristics of Class I (retrotransposons)?
Long terminal direct repeats and short flanking direct repeats at the target site.
Contains a reverse-transcriptase gene (and sometimes other genes).
Transposes through an RNA intermediate.
Examples: Ty (yeast), copia (Drosophila), Alu (human).
What are the characteristics of Class II (DNA transposons)?
Short terminal inverted repeats and short flanking direct repeats at the target site.
Contains a transposase gene (and sometimes other genes).
Transposes through DNA (either replicative or nonreplicative).
Examples: IS1 (E. coli), Tn3 (E. coli), Ac and Ds (corn), P elements (Drosophila).
What are alleles?
Alleles are different forms of a gene that exist at a specific locus (location) on a chromosome.
What is a wild type allele?
A wild type allele is the most commonly found allele in a population and typically represents the normal or standard version of a gene.
What is a variant or mutant allele?
A variant or mutant allele is different from the wild type allele. It may:
Not adversely affect the gene product.
Not result in a detectable phenotype (physical expression).
Why is purple considered the wild type in certain populations?
In certain populations, the most common allele for color (such as in flowers) is purple, which is considered the wild type because it is the most frequently observed color.
What does it mean if an organism is homozygous for an allele?
An organism is homozygous for an allele if it has identical alleles for that gene on both homologous chromosomes.
What does it mean if an organism is heterozygous for an allele?
An organism is heterozygous for an allele if it has one wild type allele and one mutant allele for a given gene.
What is an allelic series or multiple alleles?
An allelic series or multiple alleles refers to the set of known mutant alleles for a gene plus its wild type allele.
What is a wild type allele?
A wild type allele is the most common allele in a population and is considered the functionally normal version of the gene.
What are homozygotes?
Homozygotes are cells/organisms that have identical alleles for a gene of interest.
Example: FC/FC or fc/fc, where both alleles are the same on homologous chromosomes.
What are heterozygotes?
Heterozygotes are cells/organisms that have one wild type allele and one mutant allele for a gene of interest.
Example: FC/fc, where one allele is wild type (FC) and the other is a mutant (fc).
What does hemizygous mean?
Hemizygous refers to a situation where a cell/organism has only one copy of a gene, locus, or chromosomal region.
What is an example of hemizygosity due to deletion?
In a deletion scenario, the corresponding gene/locus/region is deleted on the homologous chromosome, leaving only one copy of the gene in the organism.
What is an example of hemizygosity for genes on the X or Y chromosomes?
In XY individuals (males), most genes on the X or Y chromosomes are hemizygous, meaning they only have one copy of the gene because the other chromosome is missing a second copy (i.e., males have one X chromosome and one Y chromosome).
What does dominant mean in the context of alleles?
A dominant allele is one that, in heterozygous individuals (with one copy of the allele), masks the effect of the other allele. The phenotype of these individuals is the same as those that are homozygous for the dominant allele.
What does recessive mean in the context of alleles?
A recessive allele only shows its phenotype when an individual is homozygous for that allele. In heterozygotes, the recessive allele's effect is masked by the dominant allele.
What is complete dominance?
In complete dominance, one allele completely masks the effect of the other allele in heterozygotes. The phenotype of a heterozygote is indistinguishable from a homozygous dominant individual.
How do we represent dominant and recessive alleles in notation?
Dominant alleles are typically represented by uppercase letters (e.g., FC), and recessive alleles are represented by lowercase letters (e.g., fc).
What is the relationship between the FC and fc alleles in the Flower Colour gene?
The FC allele (dominant) causes a purple flower color, and the fc allele (recessive) causes a different color. Because FC/fc and FC/FC both result in purple flowers, the FC allele is dominant over the fc allele.
What does heteroallelic mean?
Heteroallelic refers to an individual that has two different mutant alleles for the same gene, one on each chromosome.
What are the alleles in a heteroallelic organism?
In a heteroallelic organism, the alleles are different mutant alleles for a given gene. For example, fc1 and fc2 are two different mutant alleles of the Flower Colour gene, resulting in a heteroallelic combination of fc1/fc2.
What is an example of a heteroallelic individual?
An example of a heteroallelic individual would be one with fc1/fc2 alleles for the Flower Colour gene, where fc1 and fc2 are both mutant alleles different from the wild type FC allele.
What is incomplete dominance (or semi-dominance)?
Incomplete dominance occurs when the alleles of a gene do not exhibit a simple dominance/recessive relationship. Instead, the heterozygote shows an intermediate (or blended) phenotype between the two homozygous parents.
What is an example of incomplete dominance?
An example of incomplete dominance is the flower color in Four-o'clock plants:
CRed/CRed = Red petals (homozygous)
CWhite/CWhite = White petals (homozygous)
CRed/CWhite = Pink petals (heterozygous, intermediate phenotype).
What phenotype do heterozygotes exhibit in incomplete dominance?
In incomplete dominance, heterozygotes show an intermediate or blended phenotype between the two homozygous parents. For example, in the Four-o'clock plants, the heterozygote CRed/CWhite has pink petals, which is a blend of red and white.
How do heterozygotes differ from homozygotes in terms of phenotype in incomplete dominance?
In incomplete dominance, heterozygotes have an intermediate phenotype, while homozygotes express the full trait of one allele. For example, CRed/CRed produces red petals, while CWhite/CWhite produces white petals, but CRed/CWhite produces pink petals.
What is codominance?
Codominance occurs when heterozygotes express the phenotypes of both alleles simultaneously, rather than showing an intermediate phenotype. Both traits are fully expressed.
What is an example of codominance in humans?
An example of codominance is the ABO blood group system:
Blood group A has A antigens on red blood cells (RBC).
Blood group B has B antigens on RBC.
Blood group AB has both A and B antigens on RBC (codominance).
Blood group O has no antigens on RBC.
What happens in the heterozygous genotype for ABO blood groups?
In the heterozygous genotype A/B (blood group AB), both A and B antigens are expressed on the red blood cells, showing codominance.
How do A and B alleles interact with the O allele in terms of dominance?
A and B alleles are dominant over O, meaning:
A/O = Blood group A (expresses A antigens).
B/O = Blood group B (expresses B antigens).
A/B = Blood group AB (expresses both A and B antigens).
Why are dominance and recessiveness not always useful when describing mutant alleles?
Dominance and recessiveness describe the relationship between alleles but do not provide information about the type of defect that has occurred in the gene. Thus, these terms are less useful when considering the nature of the mutation itself.
What is a more useful system for classifying mutant alleles?
A more useful system considers the type of defect in the gene. This system classifies mutant alleles based on their morph (form) or functional impact, rather than just their dominance or recessiveness.
Who contributed to the classification of mutant alleles and what was their recognition?
H.J. Muller contributed significantly to radiation genetics and the classification of mutant alleles. He was awarded the Nobel Prize in 1946 for his work in this field.
What did H.J. Muller designate as the "five classes of mutant alleles"?
H.J. Muller designated five classes of mutant alleles as "morphs," meaning "form." These classifications are still used today, with some modern equivalents also being employed.
What is a Class 1: Amorph?
: A Class 1: Amorph (also known as a null mutation) refers to the complete loss of function of a gene. It can result from mutations that entirely abolish the gene's function.
What are some examples of mutations that lead to amorphs?
Examples of mutations that result in amorphs include:
Complete deletion of the entire gene.
A missense point mutation that abolishes all functions of the protein.
A nonsense point mutation that creates a truncated, non-functional protein.
Is a gene always deleted to be considered an amorph?
No, the gene does not need to be deleted to be considered an amorph. The classification is based on the phenotype (i.e., complete loss of function), not the type of molecular lesion. A missense mutation that completely loses the function of the gene can still result in an amorph.
What is an example of an amorph allele?
An example of an amorph allele is the fc- allele in flower color. Homozygous fc-/fc- plants have completely white flowers, indicating that the allele has lost the ability to make purple pigment, which is a complete loss of function.
What is a Class 2: Hypomorph?
A Class 2: Hypomorph is an allele that is partially functional but not as active as the wild-type allele. It represents a reduced function of the gene.
What is the modern equivalent of a hypomorph?
The modern equivalent of a hypomorph is a "partial loss of function" or "leaky" mutation, since the gene still functions to some degree but not fully like the wild-type allele.
What are some examples of mutations that can lead to hypomorphs?
Examples of mutations that can cause hypomorphs include:
A mutation in a regulatory element that reduces gene expression.
A point mutation that reduces the activity of the gene product but does not eliminate it entirely.
What is the key feature of a hypomorph allele compared to an amorph?
The key feature of a hypomorph is that it still retains some functional activity, whereas an amorph allele results in a complete loss of function.
What is the role of the myostatin gene in muscle growth?
Myostatin is a repressor of muscle growth, meaning it normally limits the production of muscle tissue.
What happens when there is a loss-of-function mutation in the myostatin gene?
A loss-of-function mutation in myostatin upregulates muscle production, leading to increased muscle growth.
What is the effect of a stop mutation in the myostatin gene in cattle?
In cattle, a stop mutation in the myostatin gene leads to a complete loss of function (amorph), resulting in increased muscle growth.
: What is the outcome of a point mutation in the non-coding region of the myostatin mRNA in cattle?
In cattle, a point mutation in the non-coding region of the myostatin mRNA causes a hypomorph allele, reducing the expression of myostatin and promoting more muscle growth.
How does a mutation in the non-coding part of the myostatin mRNA in sheep result in a gain-of-function?
In sheep, a mutation in the non-coding part of the myostatin mRNA creates a new function by attracting a repressor molecule, which adds a new property to the mRNA, making it a gain-of-function mutation.
What is the difference between the effects of mutations in cattle and sheep with respect to myostatin?
In cattle, mutations in myostatin typically cause loss-of-function (amorph or hypomorph), leading to more muscle growth. In sheep, a mutation in the non-coding region of the myostatin mRNA results in a gain-of-function, giving the mRNA a new property that affects muscle growth regulation.
What is a neomorph allele?
A neomorph allele is an allele that is active but has acquired a new or novel function that the wild-type gene does not have.
What is the modern equivalent of a neomorph?
The modern equivalent of a neomorph is a "gain-of-function" mutation. However, this term can also refer to hypermorphs, making it imprecise in some contexts.
What is an example of a neomorph involving an enzyme's active center?
An example of a neomorph is a mutation in the active center of an enzyme that changes its substrate specificity, giving it a new or altered function compared to the wild-type enzyme.
How can neomorph mutations in regulatory regions affect gene expression?
A neomorph mutation in a regulatory region can lead to incorrect activation of a gene in the wrong tissues or at the wrong times, causing misexpression of the gene.
What is an example of a neomorph involving a regulatory mutation related to Burkitt lymphoma?
In Burkitt lymphoma, a neomorph mutation in the regulatory region activates the c-myc gene, leading to uncontrolled cell growth, a key feature of the cancer.
What is an example of a neomorph caused by translocations?
A neomorph can result from translocations where breakpoints in genes create new hybrid genes, such as the ABL-BCR fusion gene, which causes chronic myelogenous leukemia (CML).
What are oncogenes?
Oncogenes are neomorphic alleles of cancer genes that cause uncontrolled cell growth and contribute to the development of cancer.
How do neomorphic alleles of oncogenes cause cancer?
Neomorphic alleles of oncogenes often result from mutations in the regulatory regions or structural genes, leading to new functions or misexpression that disrupt normal cell regulation and promote cancer development.
What is the role of the MYC gene in cancer?
The MYC gene codes for a transcription factor that regulates cell growth and proliferation. Mutations or misregulation of MYC can lead to uncontrolled cell division, a hallmark of cancer.
What is the role of the immunoglobulin (IG) in cancer development?
: Immunoglobulin (IG) genes, typically produced by B lymphocytes, can be involved in oncogene formation, such as in Burkitt lymphoma, where translocations cause the MYC gene to be regulated by the IG gene promoter, leading to inappropriate expression and uncontrolled growth.
How can translocations contribute to oncogene activation?
Translocations can bring the MYC gene under the control of the immunoglobulin (IG) gene's regulatory region, resulting in the overexpression of MYC, leading to cancer such as Burkitt lymphoma.
What is an antimorph?
An antimorph is an allele that not only acts as a dominant negative but also overrides the function of the wild-type allele in a heterozygous setting. It’s different from normal dominance because it disrupts the normal gene function rather than promoting it
What is the modern equivalent of an antimorph?
The modern equivalent of an antimorph is a "dominant negative" allele, which interferes with the normal function of the wild-type allele, causing a loss of function in a heterozygous state.
How do antimorphs act in a heterozygous setting?
In a heterozygous setting, antimorphs can override the function of the wild-type allele. This happens because the antimorphic allele produces a non-functional protein that disrupts the function of the wild-type protein.
What is a common example of antimorphs in protein complexes?
A common example of antimorphs is in protein dimers, where a mutated allele causes the protein to form non-functional dimers with the wild-type protein, rendering the entire complex dysfunctional. For example, in the case of a helicase, a mutant dnaB allele may prevent the helicase hexamer from functioning properly by forming defective complexes.
What happens when an antimorphic allele is present in a protein complex?
When an antimorphic allele is present, it can interfere with the function of the entire protein complex by creating non-functional dimers, which disrupt the activity of the wild-type proteins, even in heterozygotes.
What does the capital "M" represent in this context?
The capital "M" represents a dominant mutant allele, where the mutated version of the allele can override or affect the function of the wild-type allele.
What happens when the wild-type protein and mutant protein bind together in a heterozygous setting?
When the wild-type protein and mutant protein bind together, they form a non-functional dimer, which prevents the normal protein complex from functioning properly. This dominance is due to the mutant allele's ability to disrupt the wild-type protein's function.
How does the dominant mutant allele affect the function of the wild-type allele?
The dominant mutant allele can cause a loss of function in the wild-type allele by forming a non-functional dimer. As a result, the normal function of the wild-type protein is disrupted, even in a heterozygous individual.
What is a typical outcome when heterozygotes carry a mutant allele (M) and a wild-type allele (+)?
In heterozygotes carrying a mutant allele (M) and wild-type allele (+), the mutant allele can disrupt the normal protein function by interacting with the wild-type protein, leading to a non-functional dimer and affecting the phenotype.
Why is the mutant allele considered dominant in this scenario?
The mutant allele is considered dominant because it interferes with the normal function of the wild-type allele, resulting in a dominant negative effect. Even a single copy of the mutant allele can cause a loss of function in the entire protein complex.
What is heredity in biology?
Heredity is the process by which traits or characteristics are passed from parents to offspring through genetic inheritance.
Who is Gregor Mendel?
Gregor Mendel was an Augustinian priest, teacher, and the founder of the principles of heredity. He conducted groundbreaking genetic experiments with pea plants.
What was Gregor Mendel’s educational background?
Mendel had a broad science education in mathematics, botany, and plant physiology, which helped him apply the scientific method in his genetic experiments.
How did Mendel conduct his experiments?
Mendel performed breeding experiments with pea plants, studying how traits were inherited across generations.
What did Gregor Mendel discover?
Mendel discovered the fundamental principles of heredity—the laws of inheritance—without knowledge of meiosis, chromosomes, or the concept of genes.
When was Mendel’s work recognized?
Mendel’s work remained unrecognized until the 1900s, long after his death.
: Why are pea plants a good model organism for studying genetics?
Pea plants are a good model organism because they have a relatively fast generation time (~1 year), produce many offspring, and have many varieties with diverse characteristics, which allows for mathematical calculations in genetic studies.
What is the difference between a characteristic and a trait (phenotype)?
A characteristic is an attribute or feature possessed by an organism, while a trait (or phenotype) is the appearance or manifestation of that characteristic.
How many characteristics did Mendel focus on in his experiments with pea plants?
Mendel focused on 7 key characteristics that had distinct and easily discernible traits/phenotypes.
What kind of variation did Mendel focus on in his pea plant experiments?
Mendel focused on characteristics that had binary traits (traits with only two possible outcomes), rather than those with a large range of variation.
Why was Mendel successful in discovering the principles of heredity?
Mendel's success was partly due to his use of the scientific method. He made new hypotheses and tested them, rather than just describing results as others had done.
What does the term "cross" refer to in genetics?
In genetics, "cross" refers to the mating of two organisms to produce progeny, typically denoted by an "X".
How did Mendel's approach differ from other investigators at the time?
Unlike earlier investigators who merely described experimental results, Mendel used the scientific method, making hypotheses and testing them through controlled experiments.
What is the central question Mendel was trying to answer in his experiments?
How are traits passed on to offspring?
What does the term "cross" mean in the context of Mendel's experiments?
"Cross" refers to the mating of two pea plants to produce offspring (progeny), used to study inheritance patterns.
What happens when yellow and green pea plants are crossed in Mendel's experiment?
When yellow and green pea plants are crossed, all offspring are yellow because yellow is the dominant trait.
What happens when pea plants with blended traits are crossed?
When pea plants with blended traits are crossed, all offspring show yellow-green as a blended phenotype.
What are the sex organs of pea plants?
Pea plants are hermaphroditic, meaning they have both male (anthers) and female (stigma) sex organs.
What role do the anthers and stigma play in pea plant fertilization?
The anthers release pollen (male gametes), and the stigma is where the female gametes (eggs) are located. These organs work together for fertilization.
How do pea plants self-fertilize?
: Pea plants self-fertilize when pollen released from the anther enters the stigma and fertilizes the female gametes, resulting in the formation of a diploid zygote.
: How do you avoid self-fertilization when crossing two pea plants?
To avoid self-fertilization, remove the anthers from one plant before they are fully developed, ensuring no pollen is produced. This plant becomes the female in the cross.
How do you perform the actual cross between two pea plants?
To perform the cross, move pollen from the second plant's anthers (the male in the cross) to the stigma of the first plant (the female in the cross).
What happens after fertilization in the experimental cross?
The female plant produces seed pods, and the seeds within these pods are the progeny from the cross.
What is pure breeding in the context of Mendel’s experiments?
Pure breeding means that all progeny from multiple generations have the same trait. For example, Mendel’s pure breeding strains were homozygous for a trait, like yellow seed color, and would produce offspring with the same trait.
How did Mendel create pure breeding strains?
Mendel used self-fertilization for multiple generations to ensure the traits were homozygous, thus creating pure breeding strains for his experiments.
What happens when Mendel crosses pure-breeding yellow seed plants with pure-breeding green seed plants?
The F1 generation will have all yellow seeds, and when the F1 generation self-fertilizes to create the F2 generation, both yellow and green seeds will appear in a 3:1 ratio.
What is a monohybrid cross?
A monohybrid cross is a cross between parents that differ in only one trait. For example, Mendel’s cross between round and wrinkled peas.
What were the results of Mendel’s monohybrid cross?
In the F1 generation, all the progeny had round seeds. However, in the F2 generation, the wrinkled trait re-emerged. This suggests that the F1 generation carried genetic information for both round and wrinkled seeds.
What happens when the F2 generation from a monohybrid cross self-fertilizes?
In the F3 generation, we see a 3:1 ratio of round to wrinkled peas, showing that the round trait is dominant and the wrinkled trait is recessive, even though both traits are carried by the F1 generation.
What do monohybrid crosses reveal about inheritance?
They show that traits are encoded by alleles, and some alleles can be dominant over others. Mendel observed that dominant traits, like round seeds, mask the expression of recessive traits, like wrinkled seeds.
What happens in the F3 generation when F2 round parents self-fertilize?
F2 round parents produce 1/3 plants with only round peas (like the pure-breeding round parent) and 2/3 plants showing both round and wrinkled peas in a 3:1 ratio (like F1 generation). This shows that the round trait is dominant.
What happens in the F3 generation when F2 wrinkled parents self-fertilize?
: F2 wrinkled parents produce only wrinkled peas, which is the same as the pure-breeding wrinkled parent, indicating the wrinkled trait is recessive and requires two copies to be expressed.
: What conclusion did Mendel reach from his monohybrid crosses?
Each plant must possess two genetic factors (alleles) that encode a characteristic, and the re-emergence of the wrinkled trait in the F2 generation is explained by the presence of two copies of the recessive allele in the F2 generation.
What do monohybrid crosses reveal about trait inheritance and allele behavior?
Monohybrid crosses show that traits are encoded by two alleles. One allele may mask the other, as the dominant allele (e.g., round) hides the presence of the recessive allele (e.g., wrinkled). During reproduction, alleles separate, with one allele going into each gamete, and fertilization brings two alleles together, explaining why traits like wrinkled can re-emerge in later generations (F2/F3).
How is genotype nomenclature used to describe seed traits in plants?
R (capital) = Dominant round trait
r (lowercase) = Recessive wrinkled trait
RR = Homozygous round (pure-breeding)
Rr = Heterozygous round (carrying both round and wrinkled alleles)
rr = Homozygous wrinkled (pure-breeding)
What did Mendel observe in his monohybrid crosses, and what did he deduce from the 3:1 phenotype ratio?
Mendel observed a 3:1 ratio of dominant to recessive phenotypes in the F2 generation.
From this, he deduced that each individual plant carries two alleles for a given trait, and these alleles separate with equal probability into the gametes during reproduction.
What is Mendel's Principle of Segregation?
During gamete formation, two alleles of a gene segregate with equal probability, meaning each gamete receives one allele of the gene.
What happens during fertilization in relation to alleles?
When two gametes join during fertilization, the resulting diploid organism inherits one allele from each parent, forming a pair of alleles for a characteristic.
How does the Principle of Segregation relate to Meiosis I?
The segregation of alleles occurs during Meiosis I when homologous chromosomes, each carrying different alleles, are separated into different gametes.
Who proposed the Chromosome Theory of Heredity, and what does it state?
Walter Sutton proposed the Chromosome Theory of Heredity, which states that genes are located on chromosomes, and Mendel's laws of inheritance are explained by the behavior of chromosomes during meiosis.
What are homologous chromosomes, and why are they important in Mendel's Principle of Segregation?
Homologous chromosomes are chromosome pairs, one from each parent, that carry the same genes but possibly different alleles. They are important because they segregate into different gametes during meiosis, explaining the inheritance of alleles.
What is a backcross in genetic testing?
A backcross involves crossing the F1 progeny back to one of the parental genotypes to test the inheritance pattern of traits.
What was Mendel’s hypothesis regarding the dominance of tall plants?
Mendel hypothesized that tall (T) was dominant to short (t), so F1 progeny from a cross between pure-breeding tall and short plants would all be heterozygous (Tt).
: How did Mendel test his hypothesis of dominance in tall plants?
Mendel tested his hypothesis by performing a backcross: crossing F1 progeny (Tt) with a short (tt) pure-breeding plant.
What were the predicted genotypic and phenotypic ratios for the backcross between F1 progeny (Tt) and the short parental plant (tt)?
Genotypic ratio: 2 Tt : 2 tt (1:1)
Phenotypic ratio: 2 Tall : 2 Short (1:1)
What would the results of the backcross between Tt (F1) and tt (short) plants tell Mendel about his hypothesis?
If tall is dominant to short, the progeny should show a 1:1 phenotypic ratio, with half of the offspring being tall (Tt) and half being short (tt), supporting Mendel's hypothesis of tall dominance
What is a testcross in genetics?
A testcross is a genetic cross between an individual with an unknown genotype and a homozygous recessive individual to determine the genotype of the unknown individual.
What is the purpose of performing a testcross?
The purpose of a testcross is to determine whether an individual with a dominant phenotype is homozygous (TT) or heterozygous (Tt) for the trait by analyzing the offspring's phenotypes.
How do you perform a testcross?
To perform a testcross, you cross the individual with the dominant phenotype (unknown genotype) with a homozygous recessive individual (tt).
What are the possible phenotypic ratios resulting from a testcross involving a heterozygous (Tt) and homozygous recessive (tt) individual?
The phenotypic ratio for the offspring would be 1:1:
50% Tall (Tt)
50% Short (tt)
What would the phenotypic ratio be for a testcross between a homozygous dominant (TT) individual and a homozygous recessive (tt) individual?
The phenotypic ratio would be 100% Tall (Tt) because all the offspring would inherit a T allele from the dominant parent and a t allele from the recessive parent.
What is a characteristic in genetics?
A characteristic refers to a feature or attribute of an organism that can vary, such as seed shape, color, or size. (gene)
What is a trait in genetics?
A trait (or phenotype) is the visible expression or manifestation of a characteristic. For example, the trait for seed shape could be round or wrinkled.
How do alleles segregate during gamete formation?
Alleles segregate independently, with each gamete receiving one allele with equal probability.
What is the probability of a gamete receiving a specific allele?
The probability of a gamete receiving a specific allele is 1/2.
What is the formula for calculating probability?
Probability = # of times a specific outcome occurs / # of possible outcomes
Why is understanding probability useful in genetics?
Understanding probability allows you to predict more complicated genetic scenarios that a Punnett square cannot easily handle.
When do you use the multiplication rule in probability?
Use the multiplication rule when the question involves “and” (e.g., What is the probability of rolling a 4 and another 4?).
Formula: Probability = P(event 1) * P(event 2)
What is an example of applying the multiplication rule in probability?
For rolling two dice and getting a 4 and another 4:
Probability = 1/2 * 1/2 = 1/32
When do you use the addition rule in probability?
Use the addition rule when the question involves “or” (e.g., What is the probability of rolling a 3 or a 4?).
Formula: Probability = P(event 1) + P(event 2)
What is an example of applying the addition rule in probability?
For rolling a dice and getting a 3 or a 4:
Probability = 1/2 + 1/2 = 1/4
How do you calculate the genotype probability for RR in a monohybrid cross (Rr x Rr)?
P(RR) = Probability progeny will be homozygous RR (R "and" R).
Using the multiplication rule:
P(RR) = P(gamete R) x P(gamete R) = 1/2 x 1/2 = 1/4
What are the phenotype and genotype probabilities for a monohybrid cross (Rr x Rr)?
Phenotype: 3/4 round, 1/4 wrinkled (3:1 ratio)
Genotype: 1/4 RR, 1/4 rr, 1/2 Rr (1:1:2 ratio)
Use Punnett square to confirm these results.
How do you calculate the genotype probability for rr in a monohybrid cross (Rr x Rr)?
P(rr) = Probability progeny will be homozygous rr.
Using the multiplication rule:
P(rr) = P(gamete r) x P(gamete r) = 1/2 x 1/2 = 1/4
How do you calculate the genotype probability for Rr (heterozygote) in a monohybrid cross (Rr x Rr)?
There are two possible ways to achieve heterozygote genotype: Rr or rR.
Using the addition rule:
P(Rr) = P(R "and" r) + P(r "and" R)
P(Rr) = (1/2 x 1/2) + (1/2 x 1/2) = 1/4 + 1/4 = 1/2
How do you calculate the phenotype probability for round seeds in a monohybrid cross (Rr x Rr)?
Round phenotype can come from combinations of R and r alleles.
Probability calculation:
P(round) = P(R "and" r) + P(r "and" R) + P(R "and" R)
P(round) = (1/2 x 1/2) + (1/2 x 1/2) + (1/2 x 1/2) = 3/4
How do you calculate the phenotype probability for wrinkled seeds in a monohybrid cross (Rr x Rr)?
Wrinkled phenotype comes from the homozygous rr genotype.
Probability calculation:
P(wrinkled) = P(r "and" r) = (1/2 x 1/2) = 1/4
What are the two major principles revealed by Mendel’s monohybrid experiments?
Principle of Segregation (Mendel’s First Law)
Concept of Dominance
What is a dihybrid cross?
A dihybrid cross is a genetic cross that involves the inheritance of two separate characteristics (e.g., seed shape and seed color).
What do Mendel's monohybrid crosses tell us about seed shape and color inheritance?
Seed Shape: Round (R) is dominant, and wrinkled (r) is recessive.
Seed Color: Yellow (Y) is dominant, and green (y) is recessive.
What is the binomial probability formula used for calculating the probability of a specific number of successes in a fixed number of trials?
The binomial probability formula is:
𝑃( k successes) = (𝑛/𝑘)⋅𝑝^𝑘⋅(1−𝑝)^𝑛−𝑘
Where:
𝑛 is the total number of trials,
𝑘 is the number of successes,
𝑝 is the probability of success,
(𝑛/k) is the binomial coefficient.
In the Rr x Rr cross, how many trials are we considering to calculate the probability for 2 wrinkled (rr) progeny?
We are considering 3 trials (3 progeny).
What is the value of the binomial coefficient (3 2)
binomial coefficent is 3
What is the full binomial probability calculation to find the probability that 2 progeny out of 3 are wrinkled (rr) from a Rr x Rr cross?
P92 rr out of 3 porgeny) = 3 x (1/4)^2 X (3/4), the final [roabbility of wrinkled seed is 9/64
What is a dihybrid cross?
A dihybrid cross involves the inheritance of two traits, each controlled by different genes located on different chromosomes.
In a dihybrid cross, how many different types of gametes will each parent produce?
Answer: Each parent will produce 4 different gametes (since there are 2 genes with 2 alleles each: 2 x 2 = 4).
Answer: Each parent will produce 4 different gametes (since there are 2 genes with 2 alleles each: 2 x 2 = 4).
he expected phenotypic ratio is:
9 Round, Yellow (double dominant)
3 Round, Green
3 Wrinkled, Yellow
1 Wrinkled, Green (double recessive)
What does Mendel’s Second Law (Principle of Independent Assortment) state?
Mendel’s Second Law states that genes at different loci (on different chromosomes) separate independently of one another during meiosis.
When is the Principle of Independent Assortment true?
The Principle of Independent Assortment is true for genes located on different chromosomes or genes that are far apart on the same chromosome.
What is the Principle of Segregation (Mendel’s First Law)?
The Principle of Segregation states that alleles of a gene (e.g., R, r) separate independently during meiosis, specifically during the separation of homologous chromosomes.
What does the Principle of Independent Assortment explain about chromosome behavior in meiosis?
The Principle of Independent Assortment explains the independent separation of non-homologous chromosomes (and the genes they carry, like R vs Y) during meiosis.
What is the relationship between Principle of Segregation and separation of chromosomes?
The Principle of Segregation is related to the separation of homologous chromosomes during meiosis, where alleles (e.g., R, r) for a gene segregate into separate gametes.
ow do you calculate the probability of obtaining a round and yellow progeny in a dihybrid cross (e.g., Rr x Rr)?
The probability of obtaining a round and yellow progeny is the product of the probabilities of inheriting round and yellow alleles independently.
Formula:
P(round, yellow) = P(round) × P(yellow)
Because of Mendel's Second Law (Principle of Independent Assortment), these events are independent.
How can the Binomial Expansion be used in genetics?
The Binomial Expansion is used to calculate the probability of specific outcomes in situations with multiple progeny or events (e.g., a certain number of round vs. wrinkled progeny in a large cross). It helps solve probability questions with multiple outcomes by expanding the binomial expression.
What do the variables p, q, n, s, and t represent in the context of a Binomial Expansion for genetic probability?
p = probability of a specific outcome (e.g., progeny being wrinkled = 1/4)
q = probability of the opposite outcome (e.g., progeny being round = 3/4)
n = number of progeny (or number of trials)
s = number of times p occurs (e.g., number of wrinkled progeny)
t = number of times q occurs (e.g., number of round progeny)
What is the formula for Binomial Expansion?
Binomial expansion:
Probability= (n!/s!⋅t!) ⋅p ^s ⋅q ^t
Where:
n! = factorial of n
s! and t! = factorials of s and t
p = probability of one event
q = probability of the other event
What does the factorial (n!) represent in the Binomial Expansion formula?
The factorial n! represents the product of all positive integers up to n. It is used to account for all possible arrangements of events or outcomes.
Example: 5! = 5 × 4 × 3 × 2 × 1 = 120.
What is the purpose of using the Chi-square goodness of fit test in genetics?
The Chi-square goodness of fit test is used to determine whether the observed ratios of progeny differ significantly from the expected ratios, and whether the differences are due to random chance or some other biological mechanism.
What does the Chi-square test tell us?
The Chi-square test provides a way to evaluate the likelihood that the observed differences between the expected and actual data are due to chance. It helps determine if there is a significant deviation between the observed and expected results.
What is the null hypothesis in a Chi-square goodness of fit test?
The null hypothesis assumes that there is no significant difference between the observed and expected data, meaning that any difference is due to random chance.
How do you calculate Chi-square (χ²)?
χ 2=∑ (O−E) ^2/E
fter calculating the Chi-square statistic, how do you determine if the results are statistically significant?
o determine statistical significance, compare the calculated Chi-square value to a critical value from the Chi-square distribution table, based on the degrees of freedom and the desired significance level (e.g., 0.05).
If the calculated χ² is greater than the critical value, the difference is significant, and the null hypothesis is rejected.
What does a low Chi-square value suggest?
A low Chi-square value suggests that the observed and expected values are similar, and the differences could likely be due to chance, supporting the null hypothesis.