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Genetics

Summary

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Week 1 - Introduction
- Polygenic —> traits with multiple genes
- Gregor Mendel —> predictable offspring (didn’t work with polygenic)
- Friedrich Miescher —> discovered DNA in 1869
- 2 sister chromatids = 1 chromosome
• When that is split —> each bit is now a separate chromosome
- Watson & Crick —> discovered 3D model of DNA —> semiconservative —> carbon 3’
to 5’ direction (the carbon number of the ribose sugar

- Purines: A (adenosine) & G (guanine)

- Pyrimidines —> T (thymine) / U (Uracil) & C (cytosine)
- The template DNA strand reads 3’ to 5’
- DNA polymerase reads 5’ to 3’ (coding)
- Central dogma: DNA —> mRNA —> proteins
- tRNA —> brings in amino acids
- Codon —> 3 nucleotides
- Restriction enzymes —> find certain codons and cut at that specific site
- Proteome —> complete set of coded proteins in a genome
- Human genome has ~ 3.2 billion bases —> 32,000 bases actually code for something
- Splicing —> this uses a combination of a set of genes, resulting in bit variety from a
small sample

- Drosophila melanogastor —> have 4 chromosomes (include sex chromosomes)

- Wild type —> dominants, represented by +ve
- Mutant would be the recessive

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Week 2 - Mitosis and Meiosis

- Mitochondria (ATP production) and chloroplast (photosynthesis) both have their own
DNA and can duplicate, were previously not in eukaryotic cells —> endosymbiotic theory

- Nucleolus —> a dense part of the nucleus —> contains ribosomal RNA (rRNA) —>
used to make ribosomes (small and large subunits)

- Material passes through nucleus via nuclear pores

- 46 chromosomes (in somatic cells) — 23 chromosomes (in germ cells)
- Diploid = 2n —> 2 x 23 = 46
- Mitosis is responsible for growth and repair (asexual reproduction)

Mitosis
- Interphase:

• G1 —> growth and development

• S —> genome duplication
• G2 —> further growth (organelles duplicate)
- Mitosis:

• Prophase —> centrioles (spindle fibres) migrate the either end of the cell (poles),
nuclei membrane disintegrates and chromosomes are now visible

• Metaphase —> before it is prometaphase, now all chromosomes have lined up at the
metaphase plate and microtubules are connected to kinetochores (at centromere)

• Anaphase —> chromosomes are split apart into 2 sister chromatids which are now
individual chromosomes, the cohesion proteins (holding sister chromatids) are
separated by separase

• Telophase —> spindle fibres disappear, chromosomes uncondense and nuclear

membrane starts forming again

- Cytokinesis (cell division)

________________________________________________________________________

- There are 4 names based on where the centromere is: metacentric (middle),
submetacentric (slightly towards one end), acrocentric (end of chromosome),
dicentric (2 centromeres), acentric (no centromere)
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- There are 3 checkpoints:

• G1 checkpoint —> check if everything has grown properly before it starts to duplicate
its DNA (S phase)

• G2 checkpoint —> checks if the DNA has been duplicated without any errors
• Metaphase checkpoint —> checks if all the chromosomes are attached to the
spindle fibres with the kinetochore

Meiosis
- There are 2 sounds of cell division: meiosis 1 and meiosis 2 —> end up with 4 haploid
cells

- Only occurs in germ cells

- In meiosis 1, the sister chromatids are not separated —> homologous pairs are
divided into each cell

- Males —> 4 haploid cells, females —> 4 haploid cells but only 1 is usable
________________________________________________________________________

- Interphase —> the centrisomes and DNA have duplicated so we can now see them
- Prophase 1 —> go under synapsis (chromosome from each parent are coming
together), crossing over (swapping parts of their chromosomes)

- Metaphase 1 —> homologous chromosomes line up at metaphase plate, and can

assort themselves randomly (independent assortment), spindles attach to centromere

- Anaphase 1 —> pulling the homologous chromosomes apart

- Telophase 1 —> reforming nucleus and chromosome uncondense
- Cytokinesis —> cell division, end up with 2 cells
________________________________________________________________________

- Prophase 2 —> this time there is no crossing over

- Metaphase 2 —> line up at metaphase plate
- Anaphase 2 —> pulling chromosomes apart, this time each chromosome is being
pulled apart to give 2 chromosomes (which were sister chromatids before)

- Telophase 2 —> nucleus reforms and chromosome uncondense

- Cytokinesis —> cell division, now have 4 cells

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- Prophase 1 itself has 5 stages:

• Leptotene —> chromosomes condensing
• Zygotene —> each chromosome pairs with its homologue (homologous pair)
• Pachytene —> chromosomes get thicker
• Diplotene —> crossing over
• Diakinesis —> moving apart (going to metaphase plate)

∴ Synapsis and crossing over occur at prophase 1

∴ Law of independent assortment occurs at metaphase 1

- Spermatogenesis —> creating sperm cells

- Oogenesis —> creating egg, all of them are made before the female is born
• When female hits puberty —> meiosis 1 is complete
• When sperm attaches to egg —> meiosis 2 starts
- Polytene chromosomes —> oversized chromosomes that keep duplication without cell
division (used in slivery glands of drosophila as they need heaps of food to grow)

- Heterochromatin —> tightly packed chromosomes that don’t have much gene content
(low in gene content)

- Euchromatin —> less condense regions (high in gene content)

- Telomeres —> ends of chromosomes that don’t get replicated properly

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Week 3 - Mendelian Genetics

- Monohybrid cross —> a cross made by mating 2 true-breeding individuals (Aa x Aa)
- P1 —> parental generation
- F1 —> first offspring (filial)
- F2 —> seconds offspring
- 3:1 was a ratio used for when there were dominant and recessive
- Reciprocal crosses —> the cross could go both ways, so it wasn’t dependent on sex
- Mendel’s 3 postulates:
1. Unit factors in pairs —> either PP, pp, Pp

2. Dominance / recessive —> 2 factors unlike each other are responsible

3. Segregation —> the different ‘unit factors’ (alleles) are separated randomly
(Rr —> R and r)

4. Independent assortment —> during metaphase 1, the homologous chromosomes

assort independently of each other at the metaphase plate

- Monohybrid —> a hybrid that is heterozygous for a specific gene (e.g. height)
- Test cross —> an unknown genotype is crossed with a homozygous recessive

• If all offspring are Dd —> unknown genotype was DD

• If half were Dd and the other half dd —> unknown genotype was Dd
- Dihybrid cross —> a cross that is heterozygous for 2 different genes (AaBb x AaBb)
• e.g. crossing yellow green peas with wrinkled green peas
• All F1 would’ve had yellow green peas, ratio of 3:1
• F2 however have a ratio of 9:3:3:1 (when using product law for 3:1)
- Produce law —> when 2 independent events occur simultaneously, the probability of 2
of those outcomes occurring together is the produce of their individual probability

- The test cross can only be used for a dihybrid cross (use a punnett square)
- Fork-lined method is useful for large crosses, to figure out the ratio of each possibility
- If the phenotypic ratio is 3:1, the genotype would be 1:2:1
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- 2n = number of phenotypes, e.g. 22 = 4

- 3n = number of genotypes, e.g. 32 = 9
- n = number of heterozygous pair, e.g. if n = 2 —> AaBb x AaBb
- P (probability) = number of events that can happen / total number of events
- Multiplication rule —> independent events occurring simultaneously (product law)
- Addition rule —> mutually exclusive events (not occurring at the same time)
- Complete dominance —> what Mendel worked with
- Multiple alleles —> more than the typical A and B, could include 4 (ABCD)
- Pedigrees —> a diagram that shows the occurrence and appearance or phenotypes of
a particular gene or organism and its ancestors from one generation to the next

- Electrophoresis —> separating DNA based on its charge and size (the shorter / smaller
it will be, the faster it will go)

• Homozygous gives 1 band, heterozygous gives 2 bands

- Biochemical genetics —> where the genotype would affect its phenotype, e.g. AA
produce a lot of enzymes, Aa produces less, aa produces even less

- Recombinant / non-parental —> where the offspring isn’t exactly like the parents (e.g.
Mendel’s work, 50% theoretically should've been recombinants)

- Linkage —> when genes are so close, recombination occur

- Karyotype —> chromosomes ordered by size from 1 - 23

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Week 4 - Extension of Mendel

- Mendel didn’t work with sex linkage
- Crossed white eyed males x white eyed females:
• F1 was all wild type
• F2 —> males had both red and white eyes
- Sex linkage —> there are some genes that are found on the sex chromosomes (X,Y)
• e.g. colour blindness
- Crossed red eyed female x white eyed male
• F1 was all wild type
• F2 —> all females were red eyed, but males had both red and white eyes
- Incomplete dominance —> red and white colour would produce pink (mixed)

• Its phenotype would be 1:2:1 (1/4 red, 1/2 pink, 1/4 white)
• e.g. snapdragon flowers
- Codominance —> ABO or NM blood group (multiple traits can all be dominant)

• Phenotypic ratio = genotypic ratio

• ABO blood group would give rise to 4 different blood types: A, B, AB, O
- Manx cat have no tail if its heterozygous —> however its lethal

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- Agglutination —> clumping together of blood if a foreign blood enters the body
- Type AB —> universal recipient
- Type O —> universal donor
- There could be a mutation in the H substance —> A or B antigens cannot be added to
blood group AB —> appears as O type (could be very dangerous)

- Nondisjunction —> failure for sex cells for divide, can either happen in meiosis 1 or 2
- Trisomy —> a zygote having 3 copies of a single chromosome (2n + 1), e.g. trisomy 21
- Aneuploidy —> an abnormal number of chromosomes (due to nondisjunction)
- Pleiotrophy —> where a single chromosome is responsible for a number of unrelated
phenotypic effects, e.g. sickle cell anaemia

• Carriers of sickle cell anaemia is an example of incomplete dominance

- Combining dominance and codominance would have to do them individually and
apply product rule

- Could also combine codominance with the H mutation, applying product rule
- Epistasis —> where one gene can affect another but not visa versa —> albino
- All the ratios (derived from 9:3:3:1): 9:7, 12:3:1, 13:3, 9:4:3, 9:6:1, 15:1

• They all have to add up to 16

• Mendelian ratios would have to up to 4 (3:1, 1:2:1, 1:1:1:1)
- For epistasis (coat colour) there are 2 genes:
• Epistatic gene —> determines if the second gene gets applied or not,
e.g. C = present or c = absent

• Second gene —> actual pigment colour, e.g. B = black or b = brown

- Recessive epistasis —> if the epistatic gene is c = absent, it doesn’t matter how much
pigment the second gene has, it won’t get applies —> albinism

• 9:3:4 would represent epistasis

- Complementary gene action —> requires both genes (epistatic and second gene), so
if any one of those are homozygous recessive it won’t give a colour

• 9:7 would represent this

- Complementation analysis —> when there are 2 mutations that cause the same effect
but are on different places —> allows us to see whether they are alleles or not
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- e.g. wing production in drosophila

• If on different genes —> offspring will have wings
• If on same genes —> offspring will not have wings
- Expresivitiy —> the level of expression of a gene, e.g. R = red, could have various
shades of red

- Pentrance —> how much of the population actually express this gene, e.g. if all the
flowers are red —> penetrance = 100%

• Incomplete penetrace —> would show up normally as they haven’t been given that
dominant gene (penetrance = 0%), but in a pedigree we could determine if they
actually had it but just didn’t show it (if their offspring show it)

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Week 5 - Population Genetics

- Genotype frequency —> proportion of AA, Aa or aa in a population
- Phenotypic frequency —> proportion / ratio of specific phenotypes, how much is has
occurred in a single generation (e.g. red eye colour for drosophila)

- Allele frequency —> proportions of various alleles in a population

- Hardy-Weinberg principle —> factors that affect allele frequency in a population
- For the allele frequency to stay the same, 5 assumptions must be made:

• Large population size

• No mutations
• No genetic drift (migration)
• Random mating
• No selection
p+q=1
- p = frequency of dominant allele
- q = frequency of recessive allele

p2 + 2pq + q2 = 1
- p2 = pp —> homozygous dominant genotype
- 2pq = pq —> heterozygous genotype
- q2 = qq —> homozygous recessive genotype
- This represents a monohybrid cross (Aa x Bb)
- If the equation = 1 —> there is no change
- If it’s closer to 0 —> there would be more change
________________________________________________________________________

- Polymorphism —> 2 or more forms (alleles) of a gene

- Inbreeding ! —> mating between relatives (Mendel used this for his peas)

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• Every time this happens, the frequency of heterozygous genotype is recedes by

half

- Random genetic drift —> a random process in which a part of the population migrates
to a new location and causes the allele frequency to change, making it no longer a true
representation of its parents

- Bottleneck effect —> a natural disaster wipes out a large proportion of the population,
killing off maybe all the red birds in a population, only leaving the yellow birds —> as the
population now grows it will mess up the allele frequency

(look in book for examples, chi squares, gene linkage and mapping)

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Week 6 - Sex Determination and

Sex Chromosomes
- The first organisms didn’t exist as male and female
- Asexual reproduction is a lot easier as it doesn’t need a male
- Sexual reproduction developed as there was crossing over —> mixing of genes that
created diversity —> natural selection

- Sexual dimorphism —> occurring in 2 distinct forms (male and female)

- Primary sexual characteristics —> sex organs (penis and vagina)
- Secondary sexual characteristics —> changes that occur after puberty (some
organisms change their appearance completely)

- Unisexual / gonochoric —> an individual has only has male or female sex organs
- Bisexual / hermaphroditic —> an individual containing both male and female sex
organs

- Intersex —> between male and female, are usually sterile (unable to reproduce)
- Primitive sexual differentiations were either +ve or -ve

• They are morphologically the same (look identical)

• They fuse during fertilisation —> zygote —> produce +ve and -ve during meiosis
• Each corn kernel on a corn cob is an individual fertilisation event
- C. elegans are worms that are hermaphrodites (both male and female)
• They lack the Y chromosome
• During fertilisation —> 99% hermaphrodites, 1% male (used for the next generation to
make 50:50 ratio of the two

- Heterogamatic —> an organism that has 2 different sex chromosomes: males —> X,Y
- Homogamatic —> an organism that has the same sex chromosomes: females —> X,X
- Klinefelter syndrome —> having 1 or more extra X chromosomes than usual
• This isn’t really a problem as x-inactivation takes care of it (shutting down extra X
chromosomes)

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• 47,XXY — 48,XXXY — 49,XXXXY

- Turner syndrome —> the Y chromosome is missing

• 45,X (45,XO)
- Hemizygous —> if the trait is either X or Y linked
- Pseudoautosomal regions (PARs) —> on the end tips of Y chromosomes
- Male specific region (MSY) —> the non recombining region of the Y chromosome
(between the PARs)

- Sex determining region (SDY) —> what determines maleness

• Becomes active about 6-8 weeks of development, giving rise to the testis determining
factor (TDF)

- AIS (androgen insensitivity syndrome) —> a mutation on the X chromosome that

causes a male to phenotypically look like a female

• Would be sterile, and example of intersex

• It prevents the body from responding to testosterone —> looks like a female
- Primary sex ratio —> ratio of male and female as they form the zygote (hard to count)
- Secondary sex ratio —> ratio of male and female that are born
- The ratio of males is generally higher —> could be that the Y chromosome is lighter than
the X chromosome

- Barr body —> inactivation of an X chromosome (n - 1), randomly shuts down 1 of them

• Only in females
• It doesn’t explain why Turner syndrome (45,XO) and Klinefelter syndrome (46,XXY) is
not normal —> it may be that it’s first needed for fetal development

Sex determination in Drosophila

- XXY —> female
- XO —> male
• The Y chromosome is not sex determining
- It’s about the ratio of X chromosomes : autosomes

• 1:2 ratio = male —> X:2A — 2X:4A — XY:2A

• 1:1 ratio = female —> 3X:3A — XY:A
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- This means males can be 2X (homogamatic) and still be a male

- Sex limited —> traits that are limited to a specific sex
- Sex influenced —> certain traits are done better by a specific sex (horns are larger on
male sheep than female sheep, and being heterozygous means male has horns but
female doesn't

- Hermaphrodite fish have a genetically programmed sex change —> testis get smaller as
ovaries get larger

- There is no universal mode of sex determination

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Week 7 - Changes in Chromosome

Number and Structure
- If acentric (no centromere) —> the chromosome (as a whole) will end up on either side
of the cell —> could cause major problems since it doesn't divide

- If dicentric (2 centromeres) —> spindle fibres attach to both centromeres, potentially

breaking the chromosome

- Euploid —> normal number of chromosomes (2n = 46)

• Diploid (2n), triploid (3n), tetraploid (4n), polyploid
- Aneuploid —> abnormal number of chromosomes, e.g. (2n + 1) or (2n -1)
• Monosomy (2n - 1), trisomy (2n + 1), tetrasomy (2n + 2)
- Monoploid refers to the original number of polyploid series

• Wheat has 42 chromosomes and is a hexaploid species

• 6x = 42 —> x = 7 —> monoploid number
• For humans: 2x = 46 —> x = 23 —> monoploid number
- Endoreduplication —> doubling chromosome number without cell division (polytene)

• Autopolyploidy —> getting a chromosome from a single diploid cell that did not
divide it’s cell (via endoreduplication)

• Allopolyploidy —> getting a chromosome from the hybridisation of 2 different

species, which formed 1 cell, this also includes the endoreduplication + hybridisation,
so all of the genes in that 1 last cell is the combination from the other 2 species that
were mated

- Plants do go under polyploidisation (2n —> 3n —> 4n)

- Endoreduplication can be used to double the chromosomes if it an odd number —>
make them fertile if chromosome number is even

- Endopolyploid —> certain cells in an organism that is normally diploid, that are instead
polyploid

• e.g. humans are diploid (2n), but liver cells may contain tetraploid (4n)

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Trisomy (2n + 1)
- An extra copy of a large chromosome in humans is fatal
- In Datura (plant), if theres a trisomy —> there are 12 different varieties and all of them
live

- This is mainly cause by nondisjunction —> chromosomes not successfully separating

during meiosis

- Trisomy 21 causes down syndrome

- Edwards syndrome —> trisomy 18
- Patau syndrome —> trisomy 13
- Amniocentesis —> taking amniotic fluid and karyotype it to determine if there are any
chromosomal problems

- For trisomy 21 there are 3 different problems during meiosis:

• Trivalent —> trisomic chromosomes pairing abnormally
• Bivalent and univalent —> only 2 are paired, the other isn’t
- Trisomy-X —> 47,XXX (female — extra sex chromosome)
- Doubly-Y —> 47,XYY (male —Jacob’s syndrome)
- Klinefelter syndrome —> 47,XXY (male, sterile)
- Turner syndrome —> 45,XO (female, sterile)
- Fragile-X syndrome (Martin-Bell syndrome) —> trinucleotide repeat of CGG (>250
repeats —> will express it) —> X chromosome breaks down

________________________________________________________________________

Deletions
- Total amount of genetic information changes
- Deletions can be detected via a testcross to a fully mutant allele
- Terminal deletion —> a bit of the end is taken off
- Intercalary deletion —> a bit from the middle, forms a loop and breaks off
• During synapsis, since there is a missing part, the other normal sized chromosome
forms a deficiency loop to overcome the length issue

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Duplications
- Total amount of genetic information changes
- Tandem duplication —> repeated segments are adjacent

Inversions
- Total amount of genetic information stays the same
- The genetic rearrangement of the genes is reversed
- During synapsis —> loops would have to form to resolve the issue of their reversed
rearrangement

• Paracentric inversion —> loops in which centromere is not included

- resulting in: acentric and dicentric
• Pericentric inversion —> centromere is included
- resulting in: duplication and deletions —> inversion loop causes misalignment
during homologous pairing

Translocation
- Non-reciprocal translocation —> bit of 1 chromosome goes to its homologous pair
- Reciprocal translocation —> 2 chromosomes are involved
- If translocation occurs, it could still want to attach to their respective genes —>
chromosomes would have to bend to accomplish this

- 2 possible types of segregation:

• Alternate segregation —> end up with 1 normal and 1 balanced (everything is still
there but in different order)

• Adjacent segregation —> end up with cells that have deletions or duplications of a
gene

- Homozygous translocation —> both pairs of non-homozygous chromosomes go under

translocation

- Heterozygous translocation —> only 1 pair of non-homozygous chromosome goes

under translocation

- Robertsonian translocation —> 2 acrocentric chromosomes (centromere at end) will

bind together —> a whole chromosome would go missing (there would be 1 with 2)

• Down syndrome: 97% caused by nondisjunction, 3% by Robertsonian translocation

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Week 9 - Extranuclear Inheritance

- Non Mendelian
- Organelle heredity —> phenotypic characteristic was passed down from the DNA in
mitochondria and chloroplast

- Infectious heredity —> host cell passing down mutations / infections that’s passed
down

- Maternal effect —> the genes from the extracellular DNA of the mother are passed
down —> can then determine phenotype based on mothers genotype

- Nuclear DNA affects extracellular DNA so it’s are to track it

- Chlamydomonas demonstrates a uniparental mode of inheritance —> e.g. only
getting it from 1 parent, regardless of the strain (resistant or sensitive)

- Yeast will have 3 different inheritance pattern if it has a nuclear and mitochondrial
mutation —> that produce 2 phenotypes:

• Segregational petites —> a nuclear mutation, what normally would happen,

produces 1/2 petite and 1/2 normal colonies

• Neutral petites —> a mitochondrial mutation, taken from both parents and replicated
in the offspring, there would be no petite, all normal —> because the mutation is only
in the mitochondria

• Suppressive mutations —> all are petite as they have a dominant negative
mutation, the mitochondrial DNA replicate more rapidly

- Mitochondria —> derived from purple photosynthetic non-sulphur bacteria

- Chloroplast —> derived from photosynthetic cyanobacteria
- Some of the genes from these have moved from organelles —> nuclear DNA
- cpDNA and mtDNA —> both circular and lack histone proteins —> divide via binary
fission (just like the bacteria they originated from)

- cpDNA and nuclear DNA operate together —> code for photosynthesis and
translation (RNA —> proteins)

- cpDNA is larger than mtDNA —> has many non-coding (junk) and duplicated parts —>
recombination between cpDNA can occur

- Ribosomes of cpDNA and mtDNA are both different to normal ribosomes

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- Human mtDNA has 16,569 base pairs —> 13/70 proteins are needed for cellular
respiration (mostly found in the nucleus —> travelled there over time)

- Oocyte will have a lot more mtDNA —> has more work to do
• Also acts as a backup —> when a zygote is formed and if one of them is mutated, it
has a lot more to replace that (safe)

- Myoclonic epilepsy and ragged red fibre disease (MERRF) —> a mitochondrial disease
—> it can only be inherited if the mother has it (as the father cannot pass on his mtDNA)

- mtDNA mutations could be contributing to ageing

- Maternal effect —> nuclear gene of mother controls phenotype of offspring

• If male has the dominant allele, the female can only contribute to half the offspring
(doing as much as it can do, as its still recessive)

• However, If the female is has a dominant allele then all of the offspring will have her
phenotype

- The genotype of the parents producing the egg determines the phenotype

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Week 10 - DNA
- A genetic molecule must have these features:

• Store information
• Express information
• Allow for variation
• Replicate
- Kilobase (kb) —> 1,000 nucleotide pairs
- Megabase (Mb) —> 1,000,000 nucleotide pairs
- Virus (~0.1—1 Mb) —> Bacteria (1–10 Mb) —> Humans (100—1000 Mb)
- C value paradox —> there is no relation between genome size and organism
complexity

• There are eukaryotes that are more complex with less DNA content
- G value paradox —> the number of genes has little relationship with genome size
• Less complex organisms that have a smaller genome, actually have a larger gene
number compared to humans

• This is because human genome has a lot of junk DNA that doesn’t code for anything
- Alternative splicing —> single genes code for multiple proteins as they can be
rearragened in various ways

• Exons remain — introns are taken out

• Post transcriptional modification would then include taking different combinations of
that gene —> different gene products

- There are many different versions of DNA found in labs: A-DNA (more compact), B-DNA
(normal DNA), C-DNA, D-DNA, E-DNA, Z-DNA (spread out)

- Usually DNA polymerase (adds nucleotides to growing chain) is used, however an

organism with only RNA will just need RNA replicase for its replication

- Retrovirus —> uses reverse transcriptase: RNA —> DNA

- rRNA would be the around the longest, mRNA would finish its job and be reused again
- A smaller molecule will more faster than a larger, even if same weight
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- Semi-conservative DNA replication —> one strand of the DNA remains as a template
for the next strand

- Replicon —> the length of DNA since it has started replication

- In linear DNA (prokaryotes) —> there are multiple ori (origin sites) —> form a bubble
that grows out

• Reduces replication time

• Chromosomes don’t all replicate simultaneously
- DnaA —> protein that recognises a specific site in the DNA, preparing it for replication
- Nucleotide —> phosphate + sugar + base
- Nucleoside —> sugar + base
- The 4 bases can bind to the phosphate + sugar: ATP, TTP, GTP, CTP

- DNA ligase connects the newly formed DNA strand with the RNA primer
- The single stranded binding proteins hold the DNA strands, stabilising it
- Rate of mistake —> 1/10,000 base pairs
• DNA polymerase replaces those and DNA ligase seals it
- Telomere —> the repeats of nucleotides at the end of DNA —> uses a short RNA strand
to extend the 3’ end so it can finish its job (replication goes from 3’ to 5’ end)

• Mainly only found in germ-line and cancerous cells —> contributes to ageing

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Week 11 - Mutations & DNA Repair

- Mistakes are 1/10,000 — the ones that don’t get fixed are 1/billion
- Mutations can affect regulatory gene control (on/off switches)
- Spontaneous mutations —> natural mutations that are caused based on chemical or
biological changes

- Induced mutations —> mutations that occur based on extraneous factors like radiation,
UV or man made chemicals

- Mutagen —> an agent that causes genetic mutation

- Mutant —> the organism / allele / cell that shows the mutation taking effect
- Conditional mutations —> certain conditions (e.g. temperature) are needed for the
mutation to be expressed

- Unconditional mutations —> always expressed (what normally happens)

- Loss-of-function mutation —> eliminates function of gene
- Haploinsufficiency —> when a diploid organism only has half its genes working
(haplo), alone doesn’t make enough gene products —> disease

- Hypomorphic mutation —> reduces level of expression —> reduced function

- Hypermorphic mutation —> increases level of gene expression —> too much genes
produced

- Gain-of-function mutation —> dominant gene causes expression in abnormal places,

where it normally shouldn’t (gets excited), too much gene expression

- Missense mutation —> changing a codon (3 base pairs) which changes the amino acid
- Nonsense mutation —> could change the codon into a ‘stop codon’, which just codes
for stopping the production of a protein, if this is present at the beginning, it could cause
problems

- Silent mutation —> a mutation that doesn’t cause any changes, the change in the
codon still codes for the same amino acid

- Transverse mutation —> change in bases (to its complementary base — purine to
pyrimidine)

- Transition mutation —> change in bases (so it uncomplimentary base —purine to

purine)
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- Frameshift mutation —> insertion or deletion could cause the whole thing to shift up or
down

- In-frame mutation —> if 3 DNA base pairs (codon) is added in between, nothing really
changes

- Tautomeric form of purines and pyrimidines —> slightly different shape to their
nitrogenous bases —> non-complementary base pairing

- Intercalating agents —> chemicals that can nudge themselves in between base pairs
as they have their shape allows them to

- Fragile X syndrome —> mutations causing X chromosome to break down —> mental
retardation

• The X chromosome only becomes altered in the female germline —> only an
offspring of a female with this condition will develop it

• Too many repeats of CGG will cause this (>250)

- Transposable elements —> a DNA sequence that can change its position in the
genome —> causing mutations

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Week 12 - Regulation of Gene

Expression in Prokaryotes
- Inducible enzymes —> enzymes made for adapting to their environment
- Constitute enzyme —> enzymes made regardless of environmental conditions
- Repressible system —> if end product is in excess it can act as a gene expression (on/
off)

- There are 2 types of control:

• Negative control —> keeps occurring until it’s shut off
• Positive control —> inactive until it’s turned on

Lac Operon - Positive Control

- In E. Coli, it will only produce enzymes to break lactose down if theres lactose present

• Positive control
• Produces inducible enzymes (making it adapt to its changing environment)
• Lactose is the ‘inducer’
- Lac operon —> sequence of genes (lacZ, lacY, lacA) which code for proteins that
break down lactose

- However there to be lactose present to remove the repressor off the operator —> RNA
polymerase can then attach to the promoter to go down and make lactase enzymes

- lacZ codes for B-galatosidase: lactose —> galactose + glucose

- lacY codes for permease: brings lactose into the cell
- lacA codes for transacetylase: removes any toxins made

Lac Operon - Negative Control

- lacI can regulate transcription by producing a repressor molecule
- If lactose is present —> binds to repressor protein —> cannot stop the process —>
enzymes are made to break down lactose

- Now when there’s no lactose —> repressor molecule binds to operator gene (o) —>
lactase molecules aren’t made
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- If glucose is present and lactose is not —> needs a repressor molecule to stop
expression of lac operon —> inhibits cAMP from binding to catabolic-activating protein
(CAP) —> no lactase enzymes made

- If glucose is absent and lactose is present —> CAP binds to CAP-binding site —>
activates RNA polymerase —> make lactase enzymes

________________________________________________________________________

Week 12 - Regulation of Gene

Expression in Eukaryotes
- DNA rearrangement —> new genes can form, some can be lost, and can switch the
expression of the genes

- Chromatin —> DNA + histone + other proteins

- RNA polymerase and transcription (DNA —> RNA) regulatory molecules are all in the
transcription factory

- Nucleosome —> DNA and histone bundle

- There are 3 ways for chromatin remodelling:

• Alteration of DNA-histone contacts

• Alteration of DNA path (not as tight)
• Remodelling of nucleosome core particle
- DNA methylation —> adding a methyl group (CH3) to a base, usually cytosine —> most
often can repress transcription

- Eukaryotic transcription initiation (more complex) requires many regulatory factors

binding to specific DNA sequences, that are on the same side (cis)

• Promoters —> acts as recognition site for RNA polymerase

• Enhancers —> can increase transcription rates
• Silencers —> repress the amount of transcription initiators
- DNA binding domain and trans-activating domain are a few of the molecules used in
transcription

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- Alternative splicing —> multiple different forms of mRNA can be formed from an
original mRNA

- Proteome —> number of proteins a cell can make —> is not representative of the
amount of genes in a genome

- The process of translation can be altered, protein itself altered to make it stable or to
change its structure —> all changing the quality and quantity of gene product

- RNA silencing —> short RNA molecules can actually stop translation and trigger RNA
degradation (killing itself lol) —> can control gene expression

• Either virus infections impact our genes and cause this OR out cells have brought it in
via viruses and its stayed here (saying that viruses contain this)

• RNA interference (process of RNA splicing) uses a protein called Dicer:

RNA —> small interfering RNA (siRNA) + micro RNA (miRNA)

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Week 13 - Quantitative Genetics

- Quantitative means using ratios and having “markers” —> eye colour, pea shape
- Most traits are polygenic —> have a lot go genes contributing to one phenotype (unlike
Mendelian genetics)

- Multifactorial —> when both genes and environment influence it, e.g. human height
- Miristic traits —> polygenic traits in which the phenotype is counted in whole numbers,
e.g. pods may include: 1, 2 or 5 seeds, not 5.75

- Threshold traits —> are polygenic (multiple genes control it) and multifactorial
(environment and genes influence it) —> once it reaches a specific “threshold” (a
specific environmental condition) it can do a specific thing that it couldn’t otherwise

- Segregation (different alleles are separated randomly — dominant or recessive alleles)

and independent assortment (chromosome arrangement at the metaphase plate in
meiosis) still apply

• Look at punnett squares for segregation

- Additive and non-additive allele —> having more dominant allele will contribute to for
example the colour more —> monohybrid cross —> results in 3 different phenotypes:
AA, Aa, aa

• Much more complex with more alleles

- To estimate the number of distinct phenotypic classes —> analyse F2 generation
and get the fraction of the 2 extremes (homozygous dominant or recessive)

1/4n
- n = number of polygenes: Aa (1 gene, 2 alleles), AaBb (2 genes, 2 alleles each)

Extreme phenotypes Distinct phenotypic

n in F2 classes
1 1/4 3
2 1/16 5
3 1/64 7
4 1/256 9

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- Continuous traits —> there are no distinct variations —> like a gradient that increases,
e.g. human height

- Distribution of a trait —> how much of each variation is spread throughout the
population, e.g. ABO blood group —> the percentage of people having each type

• If there is a large spread —> distribution is spread out

• If there is not much variation (e.g. most people are AB) —> distribution is clustered

- So we need the mean but also the variation in the population in order to get a
distribution

- Standard error —> a measure of how much variance there is from the mean (needs
large samples)

- Heritability —> total phenotypic variation in a population due to genetic factors

(look in book for calculations)

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Week 14 - Population and

Evolutionary Genetics
- HW principle —> allelic frequencies stay constant over time unless acted upon by an
unwanted / external force

• Non-evolving population —> only if certain assumptions are met

- no mutations
- no selection
- no gene flow (migration)
- random mating
- large populations
- Inbreeding will reduce the heterozygotes by half in every next generation that is
produced

- Random genetic drift —> a natural disaster that knocks out a whole lot of the
population

• What’s left over may not be representative of the real population

- Gene pool —> all the alleles present in a population
- Best way to estimate VG (genetic variation) is to compare nucleotide sequences of
individuals in that population

- They looked at Adh (alcohol dehydrogenase gene) in drosophila —> the encoded
proteins differed by 1 amino acid at codon 192 (threonine vs lysine)

• Looked 11 individuals in 5 populations —> 43 nucleotide variations

• 14/43 was found in actual coding regions (exons)
• 1/43 lead tho that amino acid substitution

Neutral Theory of Molecular Evolution

- Most mutations that lead to amino acid replacement (as discussed above) —>
detrimental to an organism

- Most mutations are detrimental (removed), some are neutral (Ach gene mutation), and
some are favourable —> organism survives and passes it on (natural selection)
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- If individuals of all genotypes are subject to natural selection and do not have equal
rates of survival and reproductive success —> allele frequencies may change from
one generation to the next

- Natural selection is the principal force that shifts frequencies within large populations
(acts on microevolution —> marcoevolution)

- Variations in phenotype —> passed on —> produce more offspring that can survive
—> the most fit live on (survival of the fittest)

- Natural selection essentially violates HW principle —> causes change

- w = fitness —> ability to survive and reproduce

• A homozygous recessive individual that dies before reproducing —> w = 0 "

• This then causes a change in the allele frequency of the next generation
- The rate at which alleles may be removed from a population is heavily dependent on the
strength of selection

- Selection for complex traits influenced by the environment (natural selection):

• Directional selection —> one end of the

spectrum is selected for and against, e.g.
beak size in finches —> increasing (top
end) in dry years as they can eat a larger
variety of food sources

• Stabilising selection —> Intermediate

are favoured, so the extremes fade out,
e.g. human birth weight —> an
intermediate weight would be ideal, too
small may be underdeveloped, and too
heavy might cause problems (changes
the population variance)

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• Destructive selection —> both phenotypic extremes are

selected, e.g. artificial selection of drosophila

- Can see that as the 2 traits are selected for, after each
generation, the 2 extremes are selected for

- There are not many examples of destructive selection in

nature as it doesn’t happen very often —> mainly the
artificial selection —> we can select for the extremes of a
population which may be what we want

- Mutation is the only way alleles can change in a gene pool —> natural selection has to
act on that however

- Mutation rates —> number of new mutant alleles per number of gametes

• Very hard to detect due to silent mutations

- For a dominant trait, the mutation rate can be estimated (easily recognisable)

• Has to be fully expressed (can’t have variable expressivity and variable penetrance
—> which could cause it to just disappear in 1 generation, and reappearing in the
next)

• The mutation must be unique to that trait (or something else could cause it and it
won’t be trackable)

- Migration / gene flow —> can also alter gene frequency:

• If a few individuals move into a new population —> will bring with them different
alleles in that environment —> alleles frequencies change

• Dividing into populations that are separated geographically —> allele frequencies
may change over time due to environmental factors —> causing genetic drift

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