College Bio I - Exam III Study Guide – CLASSICAL GENETICS
Genetics is the study of inheritance.
Gregor Mendel
The daddy of modern genetics
Studied using common pea plants with easily observable phenotypes (or what he called “heritable factors”)
Normally these plants self-fertilize, but Mendel removed the stamen (male reproductive organ on a flower) before pollen (male gamete) was produced and cross-fertilized the ovules (female gamete) with pollen from plants with other phenotypes
He observed three generations:
o Parental (P): removed stamens and added pollen from a purple-flowered plant to a white-flowered plant o First Generation (F1): all four offspring from P are purple, plants self-fertilize to produce F2 generation o Second Generation (F2): three offspring from F1 are purple and one is white (3:1)
This was a monohybrid cross—mating between individuals with different alleles for one gene (in this case P and p for flower color, purple and white)
Showed that offspring are not a “blend” of parental traits, but instead one or the other (the leading theory at the time was that traits “blended” from generation to generation)
Conclusions from this:
o Principle of dominance: one allele is dominant over the other (recessive), masking its appearance o Principle of segregation: parents’ pairs of alleles separate and the offspring gets one allele from each
(later discovered to occur when chromosomes separate during meiosis, gametes are “half” relative to body cells)
o Principle of independent assortment: alleles are passed to offspring independently of each other, meaning new combinations not previously existing in the parents are possible and traits are not dependent on each other (ex. having purple flowers doesn’t increase or decrease the chance of having yellow peas, they are independent of each other)
Terms
dominant: more “powerful” form of an allele, masks recessive if present (capital letter, ex. P)
recessive: “weaker” form of an allele, only shows in phenotype if homozygous (lowercase letter, ex. p)
heterozygous: form of a gene where both the dominant and recessive alleles are present (ex. Pp), dominant masks recessive allele which only shows up in genotype (phenotype displayed matches the dominant allele), also called a carrier
homozygous: form of a gene in which only one form of an allele is present (ex. PP or pp) o dominant: dominant alleles only (ex. PP)
o recessive: recessive alleles only, only form of a gene in which the recessive phenotype is displayed (ex.
pp)
genotype: allelic makeup of a gene (ex. Pp, PP, or pp)
phenotype: physical characteristic of an organism based on the genotype (ex. dominant is displayed in Pp and PP, recessive only in pp), note though that recessive is not always rarer in a population (for instance, six fingers is dominant to five in humans but a much larger proportion of the population is born with five fingers
[homozygous recessive] than with six) Chromosomal Theory of Inheritance
Came from the discovery of mitosis and meiosis
States that chromosomes are the structures that carry the units of heredity (genes) Sex-Linked Traits
X-linked only appears on X chromosome but can affect both males and females, more common in males as they only have one X chromosome and thus the affected phenotype cannot be masked by the opposite genotype whereas in females XHXh for instance makes them a carrier but not affected (heterozygote)
Y-linked only appears on Y chromosome and thus only affects males, if father is affected all sons will be affected (100%), but no daughters will ever be affected as they do not have Y chromosomes (0%)
Hypertrichosis (excessive hair growth) is considered a Y-linked trait, meaning it only affects males
For X-linked to show up in a female (phenotype), they must inherit the affected allele from both their mother and their father making them homozygous for it (ex. XhXh)
X-linked affected fathers will always pass that allele on to their daughters but never to their sons (since daughters get one X from father and one X from mother, whereas sons get one Y from father and one X from mother)
Revisiting the first point, females heterozygous for X-linked traits are termed carriers (people who possess the genotype but not the phenotype, aka heterozygotes), males can never be carriers—they are either affected or not
Common X-linked disorders are red-green color blindness, hemophilia, male pattern baldness, and Duchenne and Becker’s muscular dystrophies (also due to mutation as discussed later)
Genes, which are particular segments of DNA on chromosomes, control genotypes (combinations of alleles) which control phenotypes (physical characteristics of an organism). All somatic (body) cells are diploid with 46 chromosomes in humans, whereas gametes are the only haploid cells with 23 chromosomes.
Patterns of Inheritance
Mendelian
o Probability and Punnett squares
o Each new offspring is an independent event, every new fertilization has the same probability of inheritance, regardless of siblings
Non-Mendelian
o Incomplete dominance (ex. pink flower coming from red and white parents, mixed phenotypes but still NOT blending of traits, both red and white alleles are present, pink is not its own)
o Codominance (ex. fur of a spotted cow being both distinctly black and white, not mixed)
o Heterozygosis (George Shull made corn hybrids [heterozygotes] that were stronger relative to the homozygotes, heterozygotes have a greater fitness, ex. heterozygotes for sickle cell anemia don’t have the condition but have one allele for it and are more resistant to malaria as a result)
o Pleiotropy (one gene affects multiple phenotypes, usually bad [phenylketonuria disease in humans], ex.
frizzled chicken!)
o Epistasis (multiple genes affect one phenotype, ex. lab fur color)
Blood Types
Example of codominance
Based on glycoproteins (antigens) present on the membranes of red blood cells (erythrocytes)
O (or IO if you wanna complicate it) is recessive, A and B are both dominant
A and B mask O when present, however AO and BO parents can have an O child (Punnett square this bish)
Since codominance is a thing, AB is a blood type when both A and B are inherited together (meaning both antigens are mutually present on the membrane)
Thus, there are simply four blood types: A, B, AB, and O
Ignore positive and negative, that’s a whole separate protein and it just makes it more complicated than this demonstration needs to be
Nondisjunction is when either homologous chromosomes or sister chromatids fail to properly separate during meiosis I or II, resulting in gametes having abnormal numbers of chromosomes. Cells having abnormal numbers of chromosomes is called aneuploidy, some examples being Down syndrome (trisomy-21, extra 21st chromosome) and Klinefelter syndrome (males have at least one extra X chromosome, minimum XXY). These are examples of genetic disorders.
Nucleic Acids
DNA and RNA share the bases of adenine, guanine, and cytosine; thymine is in DNA and uracil is in RNA
A and T/U are complementary, C and G are complementary
DNA is antiparallel, meaning each strand runs in opposite directions (one is 5’ to 3’, the other is 3’ to 5’)
In DNA, the sugar-phosphate “backbone” is covalently bonded (strong) while each strand is held to the other by hydrogen bonds (weak) between their nitrogenous bases
When DNA replicates, the double helix “unzips” starting from the ori (origin), where the hydrogen bonds linking the two strands are the weakest
DNA polymerase and other replication proteins show up to the party
As the double helix continues to unzip, proteins keep each strand from rejoining
New nucleotides can only be added to the 3’ end (all DNA strands are built from 5’ to 3’ as that’s the end where things are being added), meaning there is a continuous leading strand and a discontinuous lagging strand
The lagging strand exists because other molecules (RNA primers) need to be added in pieces so there is a 3’ end to be built on, since when the double helix unzips there is one 3’ end and one 5’ end
The fragments of the lagging strand are called Okazaki fragments
Telomeres are strings of repetitive nucleotide sequences at the ends of chromosomes that don’t code for a protein but rather tell replication to stop (sequence is TTAGGG in humans)
DNA replication is considered to be semiconservative as each copy produced contains one old parent strand and one new daughter strand (if it was conservative the two parent strands would reform their old double helix while the two daughter strands would form their own new double helix), think that semi=half so half of the DNA molecule produced is parent and the other half is daughter, half of the original (parent) molecule is conserved
DNA was originally called the “transforming principle” because it was concluded as being what causes
transformation of one bacteria strain to another; it is where genetic information is stored and what gets passed along to future generations
Linkage and Recombination
Genetic linkage is demonstrated by genes on a single chromosome that do not go through independent assortment (they are usually physically close together which reduces the odds of them being separated during recombination)
Crossing over during meiosis results in genetic recombination—recombinant chromosomes contain genes from both parents
Recombination frequency is the proportion of new genotypes on a chromosome that are different from those found in either parent (ex. Bb on maternal chromosome and Bb on paternal chromosome, BB can be found on offspring chromosome as a simple example), calculated by the number of recombinant offspring over the total number of offspring
A linkage map shows the relative positions of genes on chromosomes
The further genes are apart on a linkage map, the higher their recombination frequency (the closer they are, the lower their recombination frequency)
Genes with linked inheritance relative to each other (for instance purple flowers might usually have green peas) are usually close together on chromosomes; doesn’t counter the principle of independent assortment though, as they could still be separated through recombination, it just so happens that they are usually inherited together because recombination has not separated them over multiple instances
Units measuring distance on a linkage map (chromosome) are centimorgans (cM), corresponding to a recombination frequency of 0.1 or 1 out 10, are a relative measure as opposed to a set distance
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People and Experiments (KNOW ONE)
Morgan
Griffith
Avery-MacCleod-McCarty (AMM)
Hershey-Chase
Morgan
Bred red-eyed flies for two years until a mutant white-eyed fly appeared (male)
He observed three generations:
o Parental (P): One white-eyed (affected) male parent and one red-eyed (homozygous dominant) female parent
o First Generation (F1): Two male and two female offspring from P, all with red eyes (males unaffected and females heterozygous carriers)
o Second Generation (F2): One male (unaffected) and one female (heterozygous carrier) from F1 produced four offspring, one affected male (white eyes) and one unaffected male (red eyes), two red-eyed females
Demonstrated sex-linked inheritance (X-linked in this case), Morgan is credited with discovering it
Males are hemizygous for sex-linked traits, meaning the only have one allele on the X or Y chromosome (ex. XHY, hemizygous for H)
Males suffer from recessive sex-linked traits at much higher rates than females (as explained in the Sex-Linked Traits section, males only inherit one x-linked allele whereas females need two, and it cannot be masked if inherited by a male since males only have one X while females have two)
ALSO worked with autosomal inheritance, finding that some genes are linked and some are recombinant (explained under Linkage and Recombination)
Griffith
Studied two strains of pneumonia bacteria, S (smooth) and R (rough)
Found that the S strain killed mice (virulent) while the R strain did not (non-virulent)
Heat killed the S strain and found that it no longer killed mice (was no longer virulent)
Mixed heat-killed S strain with living R strain and found that it killed mice (was now virulent) o When the S strain had killed mice before, it was found in the tissue of the mice
o When the mixture of heat-killed S strain with living R strain killed mice, S strain was found in the tissue of the mice
o This meant that R strain had transformed into S strain
Conclusions from this:
o Virulence property of a bacteria is contained in a chemical, which was termed “transforming principle”
o This “transforming principle” was not affected by heat
Avery-MacCleod-McCarty (AMM)
Used same strains of pneumonia bacteria as Griffith (S and R), wanted to identify what the “transforming principle” was
Through some fancy chemistry, heat killed S strain and removed either protein, RNA, or DNA from it before mixing it with the living R strain
As a control they mixed heat-killed S strain without anything else removed with the living R strain and observed transformation (R into S) occur
Removed protein from heat-killed S strain and mixed with living R strain and transformation still occurred
Removed RNA from heat-killed S strain and mixed with living R strain and transformation still occurred
Removed DNA from heat-killed S strain and mixed with living R strain and transformation did NOT occur
Conclusion from this: DNA is the “transforming principle” that causes transformation Hershey-Chase
Studied infection between bacteriophages (viruses infecting bacteria) and bacteria cells
Used T2 virus and E. coli bacteria
Used radioactive isotopes to label protein bodies (sulfur-35) in one group and internal DNA (phosphorus-32) in the other
Infected the bacteria then separated the empty phages from the bacteria and looked for where the radioactive isotopes were
Found phosphorus-32 inside the bacteria
Showed that bacteriophages inject their host cell mostly with DNA while staying attached externally with their protein bodies, which helped to show that DNA is genetic material, protein is not
Punnett Squares
Monohybrid Cross
For this example, assume the trait is dimples and they are dominant.
Genotype ratios: 1:4 DD, 2:4 Dd, 1:4 dd Phenotype ratios: 3:4 dimples, 1:4 no dimples
Sex-Linked
For this example, assume the trait is hemophilia and it is recessive.
Remember that for sex-linked traits, ratios are given by sex.
Genotype ratios: 1:2 XHXH and 1:2 XHXh female, 1:2 XHY and 1:2 XhY male
Phenotype ratios: 2:2 unaffected female, 1:2 unaffected and 1:2 affected (hemophilic) male
Dihybrid Cross
Genotype ratios: 2:16 DDAa, 4:16 DdAa, 2:16 DDaa, 4:16 Ddaa, 2:16 ddAa, 2:16 ddaa Phenotype ratios: 6:16 express D and A, 6:16 express D and a, 2:16 express d and A, 2:16 express d and a
Note that if every genotype being crossed is heterozygous, the phenotypes will follow a set 9:3:3:1 ratio. This is not the case in the cross to the left, however, as one genotype is
homozygous recessive.
Also observe how each allele from each genotype is distributed when setting up the squares!
Pedigrees
Generations are rows
Males are squares and females are circles
Males and females producing offspring are connected with horizontal lines, who are then connected to their offspring with vertical lines
When filling in alleles, dominant are capital letters and recessive are lowercase letters
Affected is colored in
Note: progeny is synonymous with offspring
Punnett squares predict future inheritance in offspring on the basis of probability while pedigrees trace past inheritance across generations in families.
Definitions
Heterozygosis: heterozygous individuals have a greater fitness (ex. heterozygotes for sickle cell anemia do not have the condition itself but are still more resistant to malaria)
Mutation: heritable changes in the nucleotide sequence of DNA that can but do not always alter gene expression, can be passed onto other cells or offspring (not always bad though)
Allele: particular version of a gene that produces a specific phenotype, can be dominant or recessive (genotypes for a particular phenotype are composed of two alleles, ex. Dd, DD, or dd)
Point Mutations
Missense mutation
o Altered nucleotide sequence altered codon altered amino acid sequence altered protein function
o Example: sickle cell anemia which affects the protein hemoglobin, red blood cells (erythrocytes) take on a sickle shape that can be painful and cause clotting in blood vessels, is much less efficient at
transporting oxygen, largely affects African populations
Nonsense mutation
o Altered nucleotide sequence altered codon polypeptide (protein) chain terminates prematurely o Example: Duchenne’s muscular dystrophy which can be inherited genetically (X-linked [the mutation is
inherited]) or caused by a new mutation in one’s own body, is a degenerative muscle disease that affects the protein dystrophin which is integral to proper muscle contraction
Frameshift mutation
o Insertion/deletion of base base reading frame is shifted all amino acids after mutation are altered
drastic changes in protein structure and function often means no useful protein is made
o Example: Tay-Sachs disease which is a severe neurodegenerative disease because there is no enzyme to break down fatty substances within the nervous system, leads to blindness, deafness, and paralysis quickly, indicated by blue-tinted eyes or big toe deformity at birth, disproportionately affects Orthodox Jewish populations
Silent mutation
o Altered nucleotide sequence similar codon (due to redundancy in genetic code) polypeptide (protein) chain is unchanged
o Example: there are no conditions associated with silent mutations as they are “silent”—no protein is affected
Comparing and Contrasting
sex-linked vs. autosomal traits (required)
spontaneous vs. induced mutations
principle of segregation vs. independent assortment
pedigree vs. Punnett square
population vs. gene pool
Sex-linked traits are found on the gonosomes (sex chromosomes, the 23rd set of chromosomes in humans, X and Y), whereas autosomal traits are found on the autosomes (body chromosomes, the 1st through 22nd sets of chromosomes in humans). Sex-linked traits are usually expressed more often in males than females, as males are hemizygous for anything X- or Y-linked and thus express it with a single allele present. Females can be either heterozygous or homozygous dominant or recessive for only X-linked traits. An example of a sex-linked trait is hemophilia, which as would be expected is much more common in males than females. Autosomal traits can be heterozygous (Dd),
homozygous dominant (DD), or homozygous recessive (dd). They occur at more even distributions between males and females. An example of an autosomal trait is whether or not dimples are present.
Spontaneous mutations occur due to internal issues within the cell, such as meiotic problems (abnormal crossing over or incorrect breakage and rejoining), tautomeric shift (affecting the hydrogen bonding affinities of DNA bases), and DNA polymerase errors (for instance skipping checkpoints during replication). Induced mutations are caused by external influences such as exposure to mutagens (ex. ultraviolet radiation, chemicals, etc.). Both damage the DNA sequence by altering the order of nucleotides.
The principle of segregation states that parental alleles segregate (later discovered to occur during meiosis) so offspring get one allele from each parent. The principle of independent assortment states that alleles are passed to offspring independent of each other, one trait not affecting the likelihood of them inheriting another trait. Both of these principles were discovered through Daddy Mendel’s pea plant experiments.
A pedigree traces past inheritance within a family while a Punnett square predicts the inheritance of future offspring.
A population is all the members of the same species within a given area while a gene pool is all of the alleles available within a population.
Hardy-Weinberg Assumptions (KNOW TWO) 1. There is no mutation.
2. There is no differential selection among genotypes.
3. There is no gene flow.
4. Population size is infinite.
5. Mating is random.
Hardy-Weinberg Equation
p2 + 2pq + q2 = 1
p + q = 1
p = dominant allelic frequency
q = recessive allelic frequency
p2 = homozygous dominant frequency
q2 = homozygous recessive frequency
2pq = heterozygous frequency
Sometimes times both equations are needed to solve what is being asked!
For instance, if you are given that red is the dominant color in flowers and that allele has a frequency of .7 within a population, that is the p value. Say that you are solving for the percentage of heterozygotes in that population, you would then solve for q which would be .3. p2 is then .49 and q2 is .09 (Σ = .58), meaning 2pq must be .42 (you could also do 2(.7)(.3) = .42). This would mean 42% of the population is heterozygous (Rr) for flower color.
