Quiz 3 Content

5 R requirements of DNA for it to exist

1. Replicate (make more)

2. Repair (protect)

3. Recombine (evolve)

4. Read Instructions (cellular maintencance)

5. Regulate the reading (rapid environmental change)

2 fundamentals/ ground truths

1. nothing makes sense in biology without considering evolution

2. cells obey the laws of chemistry

Central Dogma

DNA → RNA → proteins

• majority of the chemistry of DNA or RNA occurs through hydroxyl groups

• each amino acid is coded for by 3 nucleotides

  • 350 amino acid residues is incodd by 1,050 base pairs of coding DNA!!!

Long-term adaptation of cellular systems

• changes in environment

• time frame: years

• includes DNA replication, DNA repair, DNA recombination

Short-term adaptation (reversible) of cellular systems

• changing environments

• time frame: seconds/minutes/days

• transcription, RNA processing, translation

Main 6 elements of the cell

P, S, C, O, N, H

4 types of non-covalent interactions

1. hydrophobic interactions

   1. water is 70% of cells, playing an important role in H-bonds

2. H-bonds

3. Ionic

4. Van der Waals

ionic bonds

• cohesion between a + charged atom and a - charged

• water + salts compete for these interactions

  • weakens them

• salt interactions

• ionic bonds DO NOT EQUAL ionic interactions

  • ex:

  • protein side chains (E, R)

H-bonds

• relatively really weak

• H+ w/ a partially positive charge interacts with an electronegative atom (slightly negative)

  • FON + S sometimes

• 2 EN atoms can share a h-bond

• water can compete w/ H-bonds which weakens them

  • examples:

    • protein secondary structure

    • DNA base pairing

Van der Waals interactions

• even weaker than H-bonds

• asymmetric electrical charges can lead to 2 atoms in proximity to be attracted to each other

  • “hand-in-a-glove”

Hydrophobic interactions

• water interacts with itself w/ H-bonds

  • forming surface tension

• Nonpolar groups avoid interactions with water, causing nonpolar groups to self-associate

  • ex:

    • interior of proteins

    • double lipid membrane

Covalent Bonds in cells

• stronger than noncovalent bonds/interactions

• stable chemical link between 2 atoms by sharing 1 or more pairs of electrons

• the amount of energy it takes to break covalent bonds depends on atoms and environment

• Enzymes are required to break covalent bonds

2 Main functions of DNA

1. Inheritance

2. Gene encoding

evolution deep dive

• RNA may have been the first genes/catalysts

  • theory: lipid vesicles containing RNA gave rise to protocells

  • protocells can self-replicate

• eukaryotic cells evolve from 3 major changes

1. evolution of linear chromosomes

2. evolution of the nucleus

3. endosymbiotic theory

   1. eukaryotic cells associating w/ photosynthetic bacterium

   2. mitochondria + chloroplasts contain circular DNA (evidence)

Viruses

• came from mobile genetic elements that exist within a cell

• bacteriophages

  • transfer genes among bacteria

  • bacteria can also take UP DNA from the environment

How does DNA deal with environmental changes?

• natural selection

• gene transcription

• DNA-methylation

  • can shut down genes temporarily

origin of life

• ~ 4 Billion Years ago

• simple microorganisms extracted en. from chem. compounds + sunlight

• utilized en. to make biomolecules from the simplest elements + compounds on the Earth’s surface

Difference between the 3 branches of the TOL

• bacteria + archaea = prokaryotes

  • lack a nucleus, small size/genome

• eukaryotes

  • have double membrane organelles'

  • larger in size/genome

Model organisms

• E. Coli → bacteria

• Arabidopsis, yeast, fruit fly, mouse, zebra fish, C. elegans, human cancer cells → eukaryotes

DNA polymers (aka chromosomes)

• pack DNA into chromatids

• we have 22 pairs + an X and a Y chromosome (XX for females)

characteristics of eukaryotic chromosomes

• linear

• contain genes

• replicaiton origin

• centromeres

• telomeres

• have introns and extrons

  • introns: transcribed but NOT TRANSLATED

  • extrons: transcribed and translated (to a protein)

characteristics of bacterial chromosomes

• circular

• contain genes

• replication origins

• centromeres

• NO telomeres, NO introns

changes in the hereditary instructions allow evolution to occur

• mutation - changes int he nucleotide seq. of DNA

  • changes the instructions for a cellular component

  • can be rarely beneficial, mostly neutral, occasionally detrimental

• wild type - unmutated cells (reference genotype)

endosymbiosis summary

• cyanobacterium engulfed by a eukaryotic cell → chloroplast

• proteobacterium engulfed by a eukaryotic cell → mitochondria

  • mitochondria have their own circular DNA that can code for their own organelle-specific translation machinery

plasmids

• small circular DNA

  • likely mini-chromosomes w/ a few genes

• can move among bacteria when they have sex

• fungi make antibiotics to kill bacteria, so there is an arms-race between plasmids and the archaea

bacteria - highly evolved, but how?

• bacterial viruses (phages) can transfer genes among bacteria

• Bacteria can also take up DNA from their environment

• they replicate rapidly

3 main functions of gene regulatory sequences

1. where to start transcription

2. where to end

3. how often to transcribe

different types of RNA (4 main)

• mRNA

  • messenger RNA

  • contain an ORF

    • ORF - open reading frame

    • series of codons that encode amino acids

• ncRNA

  • transcript that lacks a coding sequence (NONCODING)

• tRNA

  • transfer RNA

  • translates codon to amino acids on a ribosome

• rRNA

  • ribosomal RNA

    • make up a ribosome

Homologs

• proteins encoded by genes that share readily detectable sequence similarities

• similarities in genes/protein sequences can help determine phylogenetic relationships

• genes can be conserved across deep lineages

multicellularity development

• egg → stem cells → specialized cells

• specialized cells are the product of expressing specific genes

• cell signaling can trigger the expression of particular sets of genes

What are some features that distinguish a eukaryotic genome from a bacterial genome?

• linear DNA vs. circular DNA

• eukaryotic DNA have introns, bacterial genomes don’t

• eukaryotic DNA have histones

• eukaryotic genome is much larger

• eukaryotic DNA is located in the nucleus, which bacteria don’t have (in cytosol)

Why does Eukaryotic DNA compact itself?

• neutralize the negative charges of the phosphoryl groups in the DNA backbone

  • w/ cations, histones, and polyamines

• DNA has supercoiling

  • positive supercoiling tightens it

  • negative supercoiling unwinds → for DNA replication/transcription!

Topoisomerase: a type 1 mechanism

• Topiosomers

  • form of circular DNA that differ only in a topological property

    • ex: linking numbers

• Topoisomerase

  • enzyme that changes DNA supercoiling

    • resolves distortion from replication/transcription

• type 2 breaks both strands and then both are resealed

topoisomerase mechanism

KNOW THE ARROW PUSHING

1. Active site Tyrosine attacks a phosphodiester bond (breaks it)

2. enzyme changes to an open conformation

3. the unbroken strand swivels through the break in the first strand

4. The enzyme in closing position

   1. liberate 3’ hydroxyl attacks the phosphotyrosine linkage to re-ligate

      1. reform the phosphodiester bond

Nulcei acid chemistry => nucleophilic attack of hydroxyls

• a hydroxyl group attacks the p, breaking a phosphodiester bond

  • ex:

• alpha, beta, gamma numbering

Why can phosphoanydride bonds break easily?

• highly unstable

• weak electron sharing

• release the phosphate

reactions at the alpha position

• transcription

• DNA replication

• transportation

reactions at the gamma position

• kinases

• ATP hydrolysis

  • for phosphorylation

constituents of nucleic acids

• deoxyribonucleic acid (DNA)

  • hydroxyl group at the 2’ position

• ribonucleic acid (RNA)

  • hydrogen at the 2’ position