Foundations Flashcards
What percentage of the human body is made of human cells vs microbial cells?
43% (30 trillion human cells vs. 39 trillion microbial cells)
What percentage of genes in the human body are human (vs. microbiome genes)?
1% (20,000 human genes vs. 2-20 million microbial genes)
“Hygiene” hypothesis for autoimmune disease
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)
Effect of parasitic worms on allergy incidence
Childhood exposure to farm environments or chronic infection with parasitic worms decreases allergies
Effect of courses of antibiotics on risk of IBD
Linear relationship: the higher the number of courses of antibiotics, the greater the risk of inflammatory bowel disease
Post-patheolithic changes in human diet
Decrease in % of fruit in diet, highly variable % of red meat in diet (non-human primates v low % of red meat)
What is a nucleic acid?
Linear polymer of nucleotides
What is a nucleotide?
nitrogenous base + sugar + phosphate(s)
In a nucleotide, which carbon has the hydroxy group that differentiates a ribose from a deoxyribose nucleotide?
2’
In a nucleotide, to which carbon does the nitrogenousbase attach?
1’
In a nucleotide, to which carbon does the phosphate group attach?
5’
In a nucleotide, which carbon is involved in nucleic acid synthesis?
3’
What are the purines?
Adenine and Guanine (2 C/N rings)
What are the pyrimidines?
Cytosine, Uracil (RNA), and Thymine (DNA) (1 C/N ring)
What bond is formed in nucleic acid synthesis?
Phosphodiester
In what direction do nucleic acids grow?
5’ –> 3’
What molecule is released in nucleic acid polymerase synthesis?
PP (two phosphate groups), providing the energy for phosphodiester bond creation
What is the structure of the DNA double helix?
Antiparallel H-bonded strands with clockwise (right-handed) turns at 10.5 BP/turn (2 nm wide)
DNA supercoiling
Overtwisted helix = fewer BP/turn, forms (+) supercoil
Undertwisted helix = more BP/turn, forms (-) supercoil
How are supercoils removed from DNA?
Topoisomerases
What’s the difference between topoisomerase I and topoisomerase II?
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
What do topoisomerase II inhbitors do?
Freeze enzyomes on the DNA helix after nuclease activity but before ligation, creating many dsDNA breaks and leading to cell death
What drug class are bacterial Topo II inhibitors?
Antibiotics: because bacterial Topo II (DNA gyrase) differs from eukaryotic Topo II, they don’t affect eukaryotic cells
Ex. Ciprofloxacin
What drug class are eukaroytic Topo II inhibitors?
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
How many base pairs are in the human genome?
3.2 billion (haploid)
What is a karyotype?
An individual’s collection of chromosomes
How long are telomeres and what do they do?
5-12 kBP, protect the ends of the chromosome from degradation
What are centromeres and of what are they composed?
The attachment point for the mitotic spindle, composed of repeat sequences
Where does DNA replication begin?
Many sites along the chromosome, called origin sequences
How many protein-coding genes are in the haploid genome?
22,500
What proportion of the protein-coding genome is made of exons vs. introns?
10% exons, 90% introns
What proteins are contained in a histone?
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
How much DNA is in a nucleosome?
146 bp
How is chromatin fiber packaging regulated?
N-terminal tails of histone proteins (“histone tails”) extending from the nucleosome are modified:
histone acetylation ==> gene transcription
histone methylation ==? ambiguous
What are stacked loops of nucleosomes called?
Domains
What are the denser and less dense regions of chromatin called?
Less dense = euchromatin (between heterochromatin regions, genes available for transcription)
More dense = heterochromatin (Non-transrcibed: telomeres, centromeres, repetitive sequences, unexpressed genes)
Where does heterochromatin reside in the nucleus?
Binds to the lamin protein network that forms the nuclear lamina (lining of the nuclear envelope)
Where does euchromatin reside in the nucleus?
Centrally (behind the heterochromatin)
