#import "template.typ": *
#show: template.with(
  title: "Quiz 2",
  subtitle: "7.016"
)

= Lecture 9

DNA is wrapped around 8 proteins called histones (octamer), which are collectively called a nucleosome.

#define(
  title: "Chromatin"
)[
  Half DNA and half proteins, they work to give structure to DNA, and make it easier to interact with.
]

#define(
  title: "Acetylation"
)[
  The addition of an acetyl group to a histone tail. The lysine is positively charged, and the process changes it to more neutral.
]

*Euchromatin* are active and are involved in gene expression, while *heterochromatin* are inactive and reside in the centromere or at the chromosome ends.

Histone Deacetylase (HDAC) help to remove the acetyl, reducing expression. Histone Acetyltransferase (HAT) do the opposite by adding an acetyl, and increasing gene expression.

The life cycle of mRNA:

+ Exons end up in the final mRNA.
+ Exists the nucleus and presents itself to a ribosome.
+ Ribosome produces a protein.
+ Degradation.

m7G is attached to the 5' end, and helps protect against degradation. The UTR is the untranslated region. The 3' end contains a poly(A) tail which also protects from degradation.

= Lecture 10

tRNA are loaded with an amino acid and bind mRNA. Codon is on the mRNA, anticodon is on the tRNA, they bond using hydrogen bonds. Their alignment is antiparallel. There are thus $4^3 = 64$ total codons, and there are $20$ encoded amino acids. This means that there is a certain amount of redundancy.

/ START codon: AUG
/ STOP codons: UAA, UAG, UGA

The above are recognized by special proteins called release factors. Because of the wobble position, where the tRNA is less specific for the third (most 3') base of the codon, we need to have redundancy to prevent this from becoming an issue.

A *frame of translation* is essentially the mod three value with which we start our translation. It is possible to find different start codons in different frames of translation, and thus we can actually have one mRNA encoding multiple peptides.

A *mutation* is a permanent change in a nucleotide sequence. Unmutated sequences are called *wild type* sequences. The four types of mutations are listed below:

/ Silent Mutation: No change in the encoded amino acid.
/ Missense Mutation: Change in the encoded amino acid. This is a cause for sickle cell anemia.
/ Nonsense Mutation: Generating an stop codon.
/ Frameshift Mutation: Changing the modularity.

Ribosomes contain rRNA and proteins. The amino acid chains are linked through peptide bonds. tRNA is loaded with a single amino acid at the 3' end.

= Lecture 11

- Most of the genome is composed of non-coding sequences.
- Genes can be transcribed in multiple orientations.
- The transcription start site is upstream (5') relative to the translation start site.
- Each gene does not necessarily have only one start codon.
- Each gene does not necessarily have only one stop codon.
- A single codon *can* be split across two exons.
- Most genes *do* have introns (97%)
- Alternative splicing is the process of having multiple variants of the same gene by including / excluding specific exons.
- Conversation across species is highest in protein coding regions.
- Enhancers and promoters are other island of high conservation.
- It is *not* the case that all genes partake in protein coding.

Many ribosomes live on the rough endoplasmic reticulum (ER). 

#twocol(
  [
    == Prokaryotic

    - Pre nucleus.
    - *Does not* have a nucleus (karyon).
    - DNA is located in the cytoplasm.
    - *Does not* have organelles.
  ],
  [
    == Eukaryotic

    - True nucleus.
    - *Has* a nucleus (karyon).
    - DNA is located in the nucleus.
    - *Has* organelles.
  ]
)

There are actually membrane-less compartments called *condensates*. 

= Lecture 12

Somatic or body cells, retain two sets of chromosomes, and are called *diploid*. The reproductive cells however, cannot have that much information, and thus need to only contain half that data, and are therefore called *haploid*.

The *mitotic spindle* is the tool that is used for mitosis. The kinetochore at the centromere is what the mitotic spindle connects to, and pulls in opposite directions.

#twocol(
  [
    == Mitosis

    - Happens in somatic cells.
    - Follows DNA replication.
    - Equal segregation of sister chromatids.
    - Followed by 'cytokinesis', or cell division.
  ],
  [
    == Meiosis

    - Necessary to form gametes.
    - Follows DNA replication.
    - segregation of chromosomes ($2n -> 1n$)
    - Followed by 'cytokinesis', or cell division.
  ]
)

= Lecture 13

Unlinked genes follow traditional Mandelian laws, while linked genes on the same chromosome require more thought. Homologous chromosomes can also exchange DNA when they cross over at points called the chiasmata, leading to a process called recombination.

= Lecture 14

According to Mendel's second law, 50% of the progeny will be parental and 50% will not.

The genetic distance is equal to the number of recombinants over the total number of progeny.

Whatever the two parental alleles are will (if they are linked) be more likely to be together, and the recombination is less likely.

/ Forward Genetics: Start with a phenotype of interest, and try to find the gene.
/ Reverse Genetics: Start with a candidate gene, and see how that impacts the phenotypes.

= Lecture 15

#define(
  title: "Hard-Weinberg Equilibrium"
)[
  - No new mutations.
  - No natural selection.
  - No drift.
  - Random mating.
  - Infinite population size.
]

There are two sides of the coin, positive and negative / purifying selection. There is also balancing selection. 

== Random Genetic Drift

Allele frequencies change by random change. Random sampling of gametes passed down may lead to a slight bias. In a large population, this will not happen, but in a small population it may be a prevalent issue.

Phylogenetic trees show the evolutionary tree.

= Lecture 16

== How to Amplify

Bacterial plasmids can be used to amplify / replicate DNA _in vivo_.

Denature double stranded DNA at 94C, then we hybridize the complementary base pairs, and then elongate using polymerase.

== How to Sequence

Mutated DNA will cause chain termination due to the absence of the OH pair. This is called ddNTP. We can introduce this at a certain point, at which the sequence will conclude after some variable amount of time.

There are different kinds of RNA, so we can learn a lot of sequencing RNA.

== Polymorphism

Polymorphism are genetic variations in a population.

- Single Nucleotide Polymorphism (SNP) is a variation at a single nucleotide.
- Simple Sequence Repeat (SSR) Polymorphism is a variation in the length of the sequence repeat.
