Foundations

Question 1

What percentage of the human body is made of human cells vs microbial cells?

Answer 1

43% (30 trillion human cells vs. 39 trillion microbial cells)

Question 2

What percentage of genes in the human body are human (vs. microbiome genes)?

Answer 2

1% (20,000 human genes vs. 2-20 million microbial genes)

Question 3

“Hygiene” hypothesis for autoimmune disease

Answer 3

Areas with high “cleaniness” have high incidence of autoimmune disease (exact cause unknown but the human body has been selected to constantly interact w/ numerous microbial commensals/symbiants)

Question 4

Effect of parasitic worms on allergy incidence

Answer 4

Childhood exposure to farm environments or chronic infection with parasitic worms decreases allergies

Question 5

Effect of courses of antibiotics on risk of IBD

Answer 5

Linear relationship: the higher the number of courses of antibiotics, the greater the risk of inflammatory bowel disease

Question 6

Post-patheolithic changes in human diet

Answer 6

Decrease in % of fruit in diet, highly variable % of red meat in diet (non-human primates v low % of red meat)

Question 7

What is a nucleic acid?

Answer 7

Linear polymer of nucleotides

Question 8

What is a nucleotide?

Answer 8

nitrogenous base + sugar + phosphate(s)

Question 9

In a nucleotide, which carbon has the hydroxy group that differentiates a ribose from a deoxyribose nucleotide?

Answer 9

2’

Question 10

In a nucleotide, to which carbon does the nitrogenousbase attach?

Answer 10

1’

Question 11

In a nucleotide, to which carbon does the phosphate group attach?

Answer 11

5’

Question 12

In a nucleotide, which carbon is involved in nucleic acid synthesis?

Answer 12

3’

Question 13

What are the purines?

Answer 13

Adenine and Guanine (2 C/N rings)

Question 14

What are the pyrimidines?

Answer 14

Cytosine, Uracil (RNA), and Thymine (DNA) (1 C/N ring)

Question 15

What bond is formed in nucleic acid synthesis?

Answer 15

Phosphodiester

Question 16

In what direction do nucleic acids grow?

Answer 16

5’ –> 3’

Question 17

What molecule is released in nucleic acid polymerase synthesis?

Answer 17

PP (two phosphate groups), providing the energy for phosphodiester bond creation

Question 18

What is the structure of the DNA double helix?

Answer 18

Antiparallel H-bonded strands with clockwise (right-handed) turns at 10.5 BP/turn (2 nm wide)

Question 19

DNA supercoiling

Answer 19

Overtwisted helix = fewer BP/turn, forms (+) supercoil

Undertwisted helix = more BP/turn, forms (-) supercoil

Question 20

How are supercoils removed from DNA?

Answer 20

Topoisomerases

Question 21

What’s the difference between topoisomerase I and topoisomerase II?

Answer 21

Topoisomerase I: nuclease activity cuts 1 strand, enzyme allows broken strand to unwind
Topoisomerase II: nuclease activity cuts 2 strands, enzyme moves helix through the break (removes 2 twists)
Both: Ligase activity reforms the bond

Question 22

What do topoisomerase II inhbitors do?

Answer 22

Freeze enzyomes on the DNA helix after nuclease activity but before ligation, creating many dsDNA breaks and leading to cell death

Question 23

What drug class are bacterial Topo II inhibitors?

Answer 23

Antibiotics: because bacterial Topo II (DNA gyrase) differs from eukaryotic Topo II, they don’t affect eukaryotic cells
Ex. Ciprofloxacin

Question 24

What drug class are eukaroytic Topo II inhibitors?

Answer 24

Chemotherapeutics: eukaryotic Topo II is more active in dividing cells than differentiated, non-dividing cells (Topo I activity consistent) & cancers contain very rapidly dividing cells
Ex. Etoposide, Doxorubicin

Question 25

How many base pairs are in the human genome?

Answer 25

3.2 billion (haploid)

Question 26

What is a karyotype?

Answer 26

An individual’s collection of chromosomes

Question 27

How long are telomeres and what do they do?

Answer 27

5-12 kBP, protect the ends of the chromosome from degradation

Question 28

What are centromeres and of what are they composed?

Answer 28

The attachment point for the mitotic spindle, composed of repeat sequences

Question 29

Where does DNA replication begin?

Answer 29

Many sites along the chromosome, called origin sequences

Question 30

How many protein-coding genes are in the haploid genome?

Answer 30

22,500

Question 31

What proportion of the protein-coding genome is made of exons vs. introns?

Answer 31

10% exons, 90% introns

Question 32

What proteins are contained in a histone?

Answer 32

2x all: H2A, H2B, H3, H4 (8 subunits) + a linker histone (H1, not part of the octamer) which associates the local nucleosomes into a thicker, more condensed chromatin fiber

Question 33

How much DNA is in a nucleosome?

Answer 33

146 bp

Question 34

How is chromatin fiber packaging regulated?

Answer 34

N-terminal tails of histone proteins (“histone tails”) extending from the nucleosome are modified:
histone acetylation ==> gene transcription
histone methylation ==? ambiguous

Question 35

What are stacked loops of nucleosomes called?

Answer 35

Domains

Question 36

What are the denser and less dense regions of chromatin called?

Answer 36

Less dense = euchromatin (between heterochromatin regions, genes available for transcription)
More dense = heterochromatin (Non-transrcibed: telomeres, centromeres, repetitive sequences, unexpressed genes)

Question 37

Where does heterochromatin reside in the nucleus?

Answer 37

Binds to the lamin protein network that forms the nuclear lamina (lining of the nuclear envelope)

Question 38

Where does euchromatin reside in the nucleus?

Answer 38

Centrally (behind the heterochromatin)